研究者総覧

岩田 久人 (イワタ ヒサト)

  • 沿岸環境科学研究センター 教授
Last Updated :2020/11/10

研究者情報

学位

  • 博士(学術)(愛媛大学)

ホームページURL

科研費研究者番号

  • 10271652

J-Global ID

プロフィール

  • 岩田 久人(IWATA, Hisato)

    愛媛大学(Ehime University)

    沿岸環境科学研究センター(Center for Marine Environmental Studies)

    環境毒性学研究室 教授(Lab. of Environmental Toxicology, Professor)


    研究室 HP: http://ecotoxiwata.jp/(Lab HP: http://ecotoxiwata.jp/en/)

    研究室 Facebook: http://fb.com/101980470429606 (Lab FB: http://fb.com/101980470429606)

    共同利用・共同研究拠点 LaMer 案内(LaMer information): http://lamer-cmes.jp/

研究キーワード

  • 細胞内受容体   オミクス   バイオインフォマティクス   種差   感受性   エコトキシコゲノミクス   水圏環境保全学   生物遺伝子資源保全   環境化学   環境毒性学   リスク評価   環境汚染   環境分析   生態系影響評価   Ecotoxicogenomics and Proteomics   Conservation of Genomic Resources   Envirommental Toxicology   Environmental Analysis and Environmental Contamination   Environmental Risk Assessment   

研究分野

  • 環境・農学 / ランドスケープ科学
  • 環境・農学 / 環境農学
  • 環境・農学 / 生物資源保全学
  • 環境・農学 / 化学物質影響
  • 環境・農学 / 放射線影響
  • 環境・農学 / 環境政策、環境配慮型社会
  • 環境・農学 / 環境影響評価

経歴

  • 2017年04月 - 現在  愛媛大学共同利用・共同研究拠点「化学汚染・沿岸環境研究拠点」拠点長
  • 2004年11月 - 現在  愛媛大学沿岸環境科学研究センター教授
  • 2000年04月 - 2004年10月  愛媛大学沿岸環境科学研究センター准教授
  • 1999年02月 - 2000年03月  ウッズホール海洋学研究所生物部日本学術振興会 海外特別研究員
  • 1995年07月 - 2000年03月  北海道大学大学院獣医学研究科助手
  • 1994年04月 - 1995年06月  日本学術振興会特別研究員−PD (研究従事機関:愛媛大学)
  • 1992年01月 - 1994年03月  日本学術振興会特別研究員−DC (研究従事機関:愛媛大学)

所属学協会

  • Society of Toxicology   日本分子生物学会   日本生化学会   日本BICER協議会   日本環境毒性学会   日本内分泌攪乱化学物質学会   日本獣医学会   環境科学会   日本環境化学会   Society of Environmental Toxicology and Chemistry   

研究活動情報

論文

  • Kraisiri Khidkhan, Yoshinori Ikenaka, Takahiro Ichise, Shouta M.M. Nakayama, Hazuki Mizukawa, Kei Nomiyama, Hisato Iwata, Koji Arizono, Keisuke Takahashi, Keisuke Kato, Mayumi Ishizuka
    Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 239 108898 - 108898 2021年01月 研究論文(学術雑誌)
  • Kazuki Kanda, Shohei Ito, Dong-Hee Koh, Eun-Young Kim, Hisato Iwata
    Ecotoxicology and Environmental Safety 207 111263 - 111263 2021年01月 [査読有り]
     研究論文(学術雑誌)
  • Kei Nomiyama, Yusuke Tsujisawa, Emiko Ashida, Syuji Yachimori, Akifumi Eguchi, Hisato Iwata, Shinsuke Tanabe
    Environmental Science & Technology 54 18 11386 - 11395 2020年09月 [査読有り]
     研究論文(学術雑誌)
  • Dong-Hee Koh, Ji-Hee Hwang, Jae-Gon Park, Woo-Seon Song, Hisato Iwata, Eun-Young Kim
    Ecotoxicology and Environmental Safety 201 110835 - 110835 2020年09月 [査読有り]
     研究論文(学術雑誌)
  • Jiahua Guo, Jiezhang Mo, Qian Zhao, Qizhi Han, Mirella Kanerva, Hisato Iwata, Qi Li
    Environmental Pollution 264 114642 - 114642 2020年09月 [査読有り]
     研究論文(学術雑誌)
  • Yumiko Obayashi, Aya Kadoya, Naoto Kataoka, Kazuki Kanda, Su-Min Bak, Hisato Iwata, Satoru Suzuki
    Frontiers in Microbiology 11 2020年08月 [査読有り]
     研究論文(学術雑誌)
  • Mari Ochiai, Nozomi Kurihara, Masashi Hirano, Akifumi Nakata, Hisato Iwata
    Environmental Science & Technology 54 11 6832 - 6841 2020年06月 [査読有り]
     研究論文(学術雑誌)
  • Hoa Thanh Nguyen, Kimika Yamamoto, Midori Iida, Tetsuro Agusa, Mari Ochiai, Jiahua Guo, Rajendiran Karthikraj, Kurunthachalam Kannan, Eun-Young Kim, Hisato Iwata
    Science of The Total Environment 720 137568 - 137568 2020年06月 [査読有り]
     研究論文(学術雑誌)
  • Ji-Hee Hwang, Kurunthachalam Kannan, Thomas J. Evans, Hisato Iwata, Eun-Young Kim
    Environmental Science & Technology 54 3 1770 - 1781 2020年02月 [査読有り]
     研究論文(学術雑誌)
  • Kohki Takaguchi, Hiroyuki Nishikawa, Hazuki Mizukawa, Rumi Tanoue, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shouta M M Nakayama, Yoshinori Ikenaka, Tatsuya Kunisue, Mayumi Ishizuka, Shinsuke Tanabe, Hisato Iwata, Kei Nomiyama
    The Science of the total environment 688 1172 - 1183 2019年10月 [査読有り]
     研究論文(学術雑誌) 
    Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism.
  • Yoshinouchi Y, Shimizu S, Lee JS, Hirano M, Suzuki KT, Kim EY, Iwata H
    Ecotoxicology and environmental safety 181 463 - 471 2019年10月 [査読有り]
  • Kei Nomiyama, Akifumi Eguchi, Kohki Takaguchi, Jean Yoo, Hazuki Mizukawa, Tomoko Oshihoi, Shinsuke Tanabe, Hisato Iwata
    Toxicology and applied pharmacology 377 114620 - 114620 2019年08月 [査読有り]
     研究論文(学術雑誌) 
    Canis lupus familiaris (domestic dog) possess a high capacity to metabolize higher-chlorinated polychlorinated biphenyls (PCBs) to thyroid hormone (TH)-like hydroxylated PCB metabolites (OH-PCBs). As a result, the brain could be at high risk of toxicity caused by OH-PCBs. To evaluate the effect of OH-PCBs on dog brain, we analyzed OH-PCB levels in the brain and the metabolome of the frontal cortex following exposure to a mixture of PCBs (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187, and 202). 4-OH-CB202 and 4-OH-CB107 were major OH-PCBs in the brain of PCB-exposed dogs. These OH-PCBs were associated with metabolites involved in urea cycle, proline-related compounds, and purine, pyrimidine, glutathione, and amino-acid metabolism in dog brain. Moreover, adenosine triphosphate levels in the PCBs exposure group were significantly lower than in the control group. These results suggest that OH-PCB exposure is associated with a disruption in TH homeostasis, generation of reactive oxygen species, and/or disruption of oxidative phosphorylation (OXPHOS) in brain cells. Among them, OXPHOS disturbance could be associated with both disruptions in cellular amino-acid metabolism and urea cycle. Therefore, an OXPHOS activity assay was performed to evaluate the disruption of OXPHOS by OH-PCBs. The results indicated that 4-OH-CB107 inhibits the function of Complexes III, IV, and V of the electron transport chain, suggesting that 4-OH-CB107 inhibit these complexes in OXPHOS. The neurotoxic effects of PCB exposure may be mediated through mitochondrial toxicity of OH-PCBs in the brain.
  • In vitro and in silico AHR assays for assessing the risk of heavy oil-derived polycyclic aromatic hydrocarbons in fish
    Su-Min Bak, Haruhiko Nakata, Dong-Hee Koh, Jean Yoo, Hisato Iwata, Eun-Young Kim
    Ecotoxicology and Environmental Safety 181 214 - 223 2019年06月 [査読有り]
  • Hazard assessment of chemicals in avian embryos by using "OMICS" approaches: What are the challenges?
    Jiahua Guo, Hoa Thanh Nguyen, Shohei Ito, Thomas Bean, Hisato Iwata
    Integrated Environmental Assessment and Management 15 3 482 - 484 2019年04月 [査読有り]
  • The aryl hydrocarbon receptor 2 potentially mediates cytochrome P450 1A induction in the jungle crow (Corvus macrorhynchos)
    Eun-Young Kim, Naomi Inoue, Dong-Hee Koh, Hisato Iwata
    Ecotoxicology and Environmental Safety 171 99 - 111 2019年03月 [査読有り]
  • Hiroshi Ishibashi, Masashi Hirano, Eun Young Kim, Hisato Iwata
    Environmental Science and Technology 53 4 2181 - 2188 2019年01月 [査読有り]
     研究論文(学術雑誌) 
    © 2019 American Chemical Society. In this study, we assessed the binding affinities of perfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs), to the ligand-binding domains (LBDs) of Baikal seal (Pusa sibirica; bs) and human (h) peroxisome proliferator-activated receptor alpha (PPARα). An in vitro competitive binding assay showed that six PFCAs and two PFSAs could bind to recombinant bs and hPPARα LBD proteins in a dose-dependent manner. The relative binding affinities (RBAs) of PFASs to bsPPARα were as follows: PFOS > PFDA > PFNA > PFUnDA > PFOA > PFHxS > PFHpA > PFHxA. The RBAs to bsPPARα showed a significant positive correlation with those to hPPARα. In silico PPARα homology modeling predicted that there were two ligand-binding pockets (LBPs) in the bsPPARα and hPPARα LBDs. Structure-activity relationship analyses suggested that the binding potencies of PFASs to PPARα might depend on LBP binding cavity volume, hydrogen bond interactions, the number of perfluorinated carbons, and the hydrophobicity of PFASs. Interspecies comparison of the in vitro binding affinities revealed that bsPPARα had higher preference for PFASs with long carbon chains than hPPARα. The in silico docking simulations suggested that the first LBP of bsPPARα had higher affinities than that of hPPARα however, the second LBP of bsPPARα had lower affinities than that of hPPARα. To our knowledge, this is the first evidence showing interspecies differences in the binding of PFASs to PPARαs and their structure-activity relationships.
  • Guo J, Nguyen HT, Ito S, Yamamoto K, Kanerva M, Iwata H
    Ecotoxicology and Environmental Safety 165 495 - 504 2018年12月 [査読有り]
     研究論文(学術雑誌)
  • Eguchi A, Nomiyama K, Sakurai K, Kim Trang PT, Viet PH, Takahashi S, Iwata H, Tanabe S, Todaka E, Mori C
    Environmental Pollution 242 98 - 105 2018年11月 [査読有り]
     研究論文(学術雑誌)
  • Ishibashi H, Kim EY, Arizono K, Iwata H
    Environmental Science & Technology 52 20 11831 - 11837 2018年10月 [査読有り]
     研究論文(学術雑誌) 
    © 2018 American Chemical Society. We investigated the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α (bsPPARα) transactivation potencies of polybrominated diphenyl ethers (PBDEs) using an in vitro bsPPARα reporter gene assay. BDE47, BDE99, and BDE153 induced bsPPARα-mediated transcriptional activities in a dose-dependent manner. To compare bsPPARα transactivation potencies of PBDEs, perfluorooctanoic acid (PFOA)-based relative potencies (REPs), a ratio of 50% effective concentration of PFOA to the test chemical, were determined. The order of REPs of PBDEs was BDE153 (13) > BDE99 (8.1) > BDE47 (6.6) > PFOA (1.0) > BDE100, BDE154, and BDE183 (not activated). PBDEs with two bromine atoms at the ortho position showed higher bsPPARα transactivation potencies than those with three bromine atoms. Comparison of the lowest-observed-effect concentration in bsPPARα reporter gene assays revealed that BDE99 was 7-fold more potent than CB99, a polychlorinated biphenyl congener with the same IUPAC number, indicating that brominated congeners could more efficiently activate bsPPARα than chlorinated congeners. The REPs of PBDEs for bsPPARα transactivation were approximately 7- to 13-fold higher than those of perfluorochemicals (PFCs), suggesting that the effects of PBDEs on the bsPPARα signaling pathway may be superior to those of PFCs. This study provides the first evidence that PBDE congeners activate PPARα in vitro.
  • Jiahua Guo, Shohei Ito, Hoa Thanh Nguyen, Kimika Yamamoto, Hisato Iwata
    Ecotoxicology and Environmental Safety 160 94 - 103 2018年09月 [査読有り]
     研究論文(学術雑誌) 
    This work aimed at evaluating the toxic effects of in ovo exposure to phenobarbital (PB) and unveiling the mode of action by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were initially treated with saline or 1 μg PB /g egg at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At 21st day, chicks that pipped successfully were euthanized and dissected for assessing the PB caused effects on phenotypes and the liver transcriptome in both genders. In the PB treatment group, a 7% attenuation in tarsus length was found in females. While no adverse phenotypic effect on the liver somatic index (LSI) was observed, PB caused significant changes in the expressions of 52 genes in males and 516 genes in females (False Discovery Rate < 0.2, p value < 0.05, and absolute fold change > 2). PB exposure modulated the genes primarily enriched in the biological pathways of the cancer, cardiac development, immune response, lipid metabolism, and skeletal development in both genders, and altered expressions of genes related to the cellular process and neural development in females. However, mRNA expressions of chicken xenobiotic receptor (CXR)-mediated CYP genes were not induced in the PB treatment groups, regardless of males and females. On the contrary, PB exposure repressed the mRNA expressions of CYP2AC2 in males and CYP2R1, CYP3A37, and CYP8B1 in females. Although transcription factors (TFs) including SREBF1 and COUP-TFII were predicted to be commonly activated in both genders, some TFs were activated in a gender-dependent manner, such as PPARa in males and BRCA1 and IRF9 in females. Taken together, our results provided an insight into the mode of action of PB on the chicken embryos.
  • Ochiai M, Iida M, Agusa T, Takaguchi K, Fujii S, Nomiyama K, Iwata H
    Toxicological Sciences 165 1 118 - 130 2018年09月 [査読有り]
     研究論文(学術雑誌)
  • ポリ塩化ビフェニル曝露によるイヌ・ネコの甲状腺ホルモン恒常性への影響
    高口 倖暉, 野見山 桂, 西川 博之, 水川 葉月, 田上 瑠美, 草木 桃子, 横山 望, 市居 修, 滝口 満喜, 中山 翔太, 池中 良徳, 石塚 真由美, 岩田 久人, 国末 達也, 田辺 信介
    The Journal of Toxicological Sciences 43 Suppl. S245 - S245 (一社)日本毒性学会 2018年06月 [査読有り]
  • Shusaku Hirakawa, Takashi Miyawaki, Tsuguhide Hori, Jumboku Kajiwara, Susumu Katsuki, Masashi Hirano, Yuka Yoshinouchi, Hisato Iwata, Chikage Mitoma, Masutaka Furue
    Environmental Science and Pollution Research 25 17 16455 - 16463 2018年06月 [査読有り]
     研究論文(学術雑誌) 
    In what has become known as the Yusho incident, thousands of people in western Japan were poisoned by the accidental ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds. In this study, we investigated the accumulation patterns of 69 PCB congeners in the blood of Yusho patients in comparison with those of non-exposed controls. The blood samples were collected at medical check-ups in 2004 and 2005. To compare the patterns of PCB congeners, we calculated the concentration ratio of each congener relative to the 2,2′,4,4′,5,5′-hexaCB (CB153) concentration. The concentration ratios of tetra- and penta-chlorinated congeners in the blood of Yusho patients were significantly lower than those of controls. To examine the cytochrome P450 (CYP)-dependent metabolic potential of the 2,3′,4,4′5-pentaCB (CB118), CB153, and 2,3,3′,4,4′5-hexaCB (CB156) congeners, we conducted PCB-CYP (CYP1A1, CYP1A2, CYP2A6, and CYP2B6) docking simulation by in silico analysis. The docking models showed that human CYP1A1, CYP2A6, and CYP2B6 isozymes have the potential to metabolize CB118 and CB153. On the other hand, it was inferred that CB156 is difficult to be metabolized by these four CYP isozymes. These results indicate that CYP1 and CYP2 isozymes may be involved in the characteristic accumulation patterns of PCB congeners in the blood of Yusho patients.
  • Jiahua Guo, Shohei Ito, Hoa Thanh Nguyen, Kimika Yamamoto, Rumi Tanoue, Tatsuya Kunisue, Hisato Iwata
    Toxicology and Applied Pharmacology 347 23 - 32 2018年05月 [査読有り]
     研究論文(学術雑誌) 
    Triclosan (TCS), a commonly used antimicrobial compound, has recently been detected in the eggs of wild avian species. Exposure to TCS in rodents is known to interfere with thyroid hormone (TH), disrupt immune responses and cause liver disease. However, no attempt has been made to clarify the effects of TCS in avian species. The aim of this study is therefore to evaluate the toxic effects of in ovo exposure to TCS and explore the molecular mechanism by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were treated with graded concentration of TCS (0.1, 1 and 10 μg/g egg) at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At the administration of 10 μg TCS/g egg, embryo mortality increased from 20% in control to 37% accompanied with 8% attenuation in tarsus length. While liver somatic index (LSI) in TCS treatments was enhanced, statistical difference was only observed at the treatment of 0.1 μg TCS/g egg in females. The up-regulation of several crucial differentially expressed genes (DEGs) in transcriptome analysis suggested that TCS induced xenobiotic metabolism (e.g. CYP2C23a, CYP2C45 and CYP3A37 in males CYP2C45 in females) and activated the thyroid hormone receptor (THR) - mediated downstream signaling (e.g. THRSPB and DIO2 in males THRSPB in females). In females, TCS may further activate the lipogenesis signaling (e.g. ACSL5, ELOVL2) and repress the lipolysis signaling (e.g. ABHD5, ACAT2). A battery of enriched transcription factors in relation to these TCS-induced signaling and phenotypes were found, including activated SREBF1, PPARa, LXRa, and LXRb in males and activated GLI2 in females COUP-TFII was predicted to be suppressed in both genders. Finally, we developed adverse outcome pathways (AOPs) that provide insights into the molecular mechanisms underlying the alteration of phenotypes.
  • Maribet Gamboa, Maria Claret Tsuchiya, Suguru Matsumoto, Hisato Iwata, Kozo Watanabe
    ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY 96 3 2017年11月 [査読有り]
     研究論文(学術雑誌) 
    Proteome variation among natural populations along an environmental gradient may provide insights into how the biological functions of species are related to their local adaptation. We investigated protein expression in five stream stonefly species from four geographic regions along a latitudinal gradient in Japan with varying climatic conditions. The extracted proteins were separated by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption/ionization of time-of-flight (MALDI TOF/TOF), yielding 446 proteins. Low interspecies variation in the proteome profiles was observed among five species within geographical regions, presumably due to the co-occurring species sharing the environments. However, large spatial variations in protein expression were found among four geographic regions, suggesting strong regulation of protein expression in heterogeneous environments, where the spatial variations were positively correlated with water temperature. We identified 21 unique proteins expressed specifically in a geographical region and six common proteins expressed throughout all regions. In warmer regions, metabolic proteins were upregulated, whereas proteins related to cold stress, the photoperiod, and mating were downregulated. Oxygen-related and energy-production proteins were upregulated in colder regions with higher altitudes. Thus, our proteomic approach is useful for identifying and understanding important biological functions related to local adaptations by populations of stoneflies.
  • Jiahua Guo, Hisato Iwata
    ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 143 111 - 119 2017年09月 [査読有り]
     研究論文(学術雑誌) 
    The occurrence of antimicrobial agent triclosan (TCS) in the global aquatic and terrestrial environment is an emerging concern. While risk assessment for TCS is available in certain countries, no studies have attempted to assess the risk of TCS worldwide. This could be due to lack of method to characterize the global exposure. The present study therefore proposed a probabilistic-based approach to approximate the percent-ranked measured environmental concentrations (MECs) by estimating exposure concentration distribution (ECD) for different environmental compartments on a global scale, incorporating approximate 1200 single MECs. Hazard of TCS was assessed from species sensitivity distribution as well as predicted no effect concentrations (PNECs) derived from ecotoxicological and toxicological endpoints. We draw on experiences from previous risk assessment exercises and present a holistic approach for characterizing the risk of TCS to microorganism in sewage treatment plant, aquatic and soil organisms, avian and mammalian species, and humans. Using the approach, we estimated risk of TCS to organisms dwelling in sediment and living in surface waters, and the risk quotients (MEC/PNEC) were within the range of 0.95-33.3 and 0.49-9.5, respectively. While the risk quotients for other environmental compartments were below a value of 1, there are large uncertainties likely due to an insufficient dataset of exposure and hazard of TCS.
  • Mari Ochiai, Kei Nomiyama, Tomohiko Isobe, Tadasu K. Yamada, Yuko Tajima, Ayaka Matsuda, Akira Shiozaki, Takashi Matsuishi, Masao Amano, Hisato Iwata, Shinsuke Tanabe
    MARINE ENVIRONMENTAL RESEARCH 128 124 - 132 2017年07月 [査読有り]
     研究論文(学術雑誌) 
    This study investigated the accumulation of polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated analogues (OH-PBDEs and MeO-PBDEs) in the blood of harbor porpoises, Dall's porpoises, and finless porpoises stranded or bycaught in Japanese coastal waters and in the North Pacific Ocean. Moreover, we suggested the origins of these contaminants and the factors affecting their pattern of accumulation. Levels of PBDEs in Dall's porpoises were one order of magnitude greater than those in the other species. OH-PBDE and MeO-PBDE levels were comparable to those of PBDEs. However, no correlation was found between the levels of OH-PBDEs and PBDEs, whereas a strong correlation was found between that of OH-PBDEs and MeO-PBDEs (p < 0.001). 6OH-BDE47, reported compound bio-synthesized by marine low-trophic level organisms, was the dominant congener. These results suggest that PBDEs found in these porpoise species derive from flame retardants, but OH-PBDEs and MeO-PBDEs are mainly of natural origins. (C) 2016 Elsevier Ltd. All rights reserved.
  • Hoa Thanh Nguyen, Maria Claret Lauan Tsuchiya, Jean Yoo, Midori Iida, Tetsuro Agusa, Masashi Hirano, Eun-Young Kim, Tatsuhiko Miyazaki, Masato Nose, Hisato Iwata
    ARCHIVES OF TOXICOLOGY 91 4 1763 - 1782 2017年04月 研究論文(学術雑誌) 
    Dioxins cause various toxic effects through the aryl hydrocarbon receptor (AHR) in vertebrates, with dramatic species and strain differences in susceptibility. Although inbred mouse strains C3H/HeJ-lpr/lpr (C3H/lpr) and MRL/MpJ-lpr/lpr (MRL/lpr) are known as dioxin-sensitive and dioxin-resistant mice, respectively, the molecular mechanism underlying this difference remains unclear. The difference in the hepatic proteome of the two mouse strains treated with vehicle or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) was investigated by a proteomic approach of two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF). To confirm the strain-difference in response to TBDD treatment, cytochrome P450 (CYP) 1A1 and 1A2 protein levels were measured in both strains. A dose of 10 A mu g/kg body weight of TBDD induced hepatic CYP1A1 and CYP1A2 expression in both strains, but the expression levels of both CYP1A proteins were higher in C3H/lpr mice than in MRL/lpr mice, supporting that C3H/lpr mice are more sensitive to dioxins than MRL/lpr mice. Proteins that were more induced or suppressed by TBDD treatment in C3H/lpr mice were successfully identified by 2-DE and MALDI-TOF/TOF, including proteins responsible for AHR activation through production of endogenous ligands such as aspartate aminotransferase, indolethylamine N-methyltransferase, and aldehyde dehydrogenases, as well as proteins reducing oxidative stress, such as superoxide dismutase and peroxiredoxins. Taken together, our results provide insights into the molecular mechanism underlying the high dioxin susceptibility of the C3H/lpr strain, in which AHR activation by TBDD is more prompted by the production of endogenous ligands, but the adaptation to oxidative stress is also acquired.
  • Su-Min Bak, Midori Iida, Anatoly A. Soshilov, Michael S. Denison, Hisato Iwata, Eun-Young Kim
    ARCHIVES OF TOXICOLOGY 91 1 301 - 312 2017年01月 研究論文(学術雑誌) 
    The toxic effects of dioxins and related compounds (DRCs) are mediated by the aryl hydrocarbon receptor (AHR). Our previous study identified AHR1 and AHR2 genes from the red seabream (Pagrus major). Moreover, we found that AHR2 mRNA levels were notably elevated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in the early life stage of red seabream embryos, while AHR1 mRNA level was not altered. In this study, to investigate the regulatory mechanism of these AHR transcripts, we cloned and characterized 5'-flanking regions of AHR1 and AHR2 genes. Both of the 5'-flanking regions in these AHR genes contained three potential xenobiotic-responsive elements (XREs). To assess whether the 5'-flanking region is transactivated by rsAHR1 and rsAHR2 proteins, we measured the transactivation potency of the luciferase reporter plasmids containing the 5'-flanking regions by AHR1 and AHR2 proteins that were transiently co-expressed in COS-7. Only reporter plasmid (pGL4-rsAHR2-3XREs) that contained three putative XRE sites in the 5'-flanking region of AHR2 gene showed a clear TCDD dose-dependent transactivation by AHR1 and AHR2 proteins. TCDD-EC50 values for the rsAHR2-derived XRE transactivation were 1.3 and 1.4 nM for AHR1 and AHR2, respectively. These results suggest that the putative XREs of AHR2 gene have a function for AHR1- and AHR2-mediated transactivation, supporting our in ovo observation of an induction of AHR2 mRNA levels by TCDD exposure. Mutations in XREs of AHR2 gene led to a decrease in luciferase induction. Electrophoretic mobility shift assay showed that XRE1, the closest XRE from the start codon in AHR2 gene, is mainly responsible for the binding with TCDD-activated AHR. This suggests that TCDD-activated AHR1 and AHR2 up-regulate the AHR2 mRNA levels and this auto-induced AHR2 may amplify the signal transduction of its downstream targets including CYP1A in the red seabream.
  • In-Sung Kim, Ji-Hee Hwang, Masashi Hirano, Hisato Iwata, Eun-Young Kim
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 187 1 - 9 2016年09月 研究論文(学術雑誌) 
    Aryl hydrocarbon receptor (AHR) is well conserved from invertebrates to vertebrates, and it mediates the toxic effects of exogenous ligands, including dioxins. Recent studies reported that AHRs activated by endogenous ligands play critical roles in mammalian physiological homeostasis. Avian species possess at least two AHR isoforms (AHR1 and AHR2), which exhibit species-and isoform-specific transactivation potencies to exogenous ligands, whereas mammals possess a single AHR. To delineate the profiles and roles of endogenous ligands for avian AHR isoforms, we investigated in vitro transactivation potencies of avian AHRs (AHR1 and AHR2 from the jungle crow, Corvus macrorhynchos; common cormorant, Phalacrocorax carbo; and black-footed albatross, Phoebastria nigripes) treated with the endogenous tryptophan metabolites 6-formylindolo [3,2-b] carbazole (FICZ), L-kynurenine (L-Kyn), kynurenic acid (KYNA), and indoxyl sulfate (IS). Furthermore, we analyzed the binding mode of these ligands to each avian AHR isoform by in silico docking simulations. The EC50 of FICZ (0.009-0.032 nM) was similar regardless of the species or isoform of AHR. The estimated in silico binding mode of FICZ to AHRs was well conserved in both isoforms. The transactivation potencies of avian AHRs to other tryptophan metabolites were 10(5)-10(7) fold lower than those for FICZ, and EC50 values varied in a species and isoform-specific manner. This was consistent with poor conservation of the binding mode of L-Kyn, KYNA, and IS predicted in in silico docking simulations. Our results suggest that in avian species, FICZ is the most potent endogenous AHR ligand, and that AHR1 and AHR2 are physiologically functional. (C) 2016 Published by Elsevier Inc.
  • Midori Iida, Satoshi Fujii, Masaya Uchida, Hiroshi Nakamura, Yoshihiro Kagami, Tetsuro Agusa, Masashi Hirano, Su-Min Bak, Eun-Young Kim, Hisato Iwata
    AQUATIC TOXICOLOGY 177 156 - 170 2016年08月 研究論文(学術雑誌) 
    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces a broad spectrum of toxic effects including craniofacial malformation and neural damage in fish embryos. These effects are mainly mediated by the aryl hydrocarbon receptor (AHR). However, the mode of action between TCDD-induced AHR activation and adverse outcomes is not yet understood. To provide a comprehensive picture of the AHR signaling pathway in fish embryos exposed to TCDD, red seabream (Pagrus major) embryos were treated with graded concentrations of TCDD (0.3-37 nM) in seawater, or with a mixture of TCDD and 500 nM CH223191, an AHR-specific antagonist. The transcriptome of red seabream embryos was analyzed using a custom-made microarray with 6000 probes specifically prepared for this species. A Jonckheere-Terpstra test was performed to screen for genes that demonstrated altered mRNA expression levels following TCDD exposure. The signals of 1217 genes (as human homologs) were significantly altered in a TCDD concentration-dependent manner (q-value < 0.2). Notably, the TCDD-induced alteration in mRNA expression was alleviated by co-exposure to CH223191, suggesting that the mRNA expression level of these genes was regulated by AHR. To identify TCDD-activated pathways, the microarray data were further subjected to gene set enrichment analysis (GSEA) and functional protein-protein interaction (PPI) network analysis. GSEA demonstrated that the effects of TCDD on sets of genes involved calcium, mitogen-activated protein kinase (MAPK), actin cytoskeleton, chemokine, T cell receptor, melanoma, vascular endothelial growth factor (VEGF), axon guidance, and renal cell carcinoma signaling pathways. These results suggest the hypotheses that TCDD induces immunosuppression via the calcium, MAPK, chemokine, and T cell receptor signaling pathways, neurotoxicity via VEGF signaling, and axon guidance alterations and teratogenicity via the dysregulation of the actin cytoskeleton and melanoma and renal cell carcinoma signaling pathways. Furthermore, the PPI network analysis indicated that the adverse outcome pathways of TCDD in the embryos might be propagated through several hub genes such as cell division control protein 42, phosphoinositide-3-kinase regulatory subunit 1, and guanine nucleotide binding proteins. Understanding these pathways potentially allows for exploring the adverse outcome pathway of the effects of TCDD on the red seabream embryos. (C) 2016 Elsevier B.V. All rights reserved.
  • Ji-Hee Hwang, Jin-Young Park, Hae-Jeong Park, Su-Min Bak, Masashi Hirano, Hisato Iwata, Young-Suk Park, Eun-Young Kim
    SCIENTIFIC REPORTS 6 2016年06月 研究論文(学術雑誌) 
    The aryl hydrocarbon receptor (AHR) mediates dioxin toxicities. Several studies have suggested that two amino acid residues corresponding to the 324th and 380th positions in the ligand binding domain (LBD) of the chicken AHR1 (Ile_Ser as high sensitivity, Ile_Ala as moderate sensitivity, and Val_Ala as low sensitivity), could be an important factor determining dioxin sensitivity in avian species. Here, we analyzed the association between ecological factors and AHR1 LBD genotypes of 113 avian species. Cluster analyses showed that 2 major clusters and sub-clusters of the cluster 3 were associated with specific AHR1 genotypes depending on the food, habitat, and migration of the animal. The majority of the species with Ile_Ala type were the Passeriformes, which are omnivorous or herbivorous feeders in the terrestrial environment. The species with Val_Ala type was primarily composed of raptors and waterbirds, which have been exposed to naturally occurring dioxins. An in vitro reporter gene assay revealed that the sensitivity to a natural dioxin, 1,3,7-tribromodibenzo-p-dioxin was in the order of Ile_Ser > Ile_Ala > Val_Ala. These results suggest that ecological factors related to the exposure of natural dioxins contribute to natural selection of the avian AHR1 genotype, which consequently leads to different sensitivity to man-made dioxins.
  • Junko Fujihara, Toshihiro Yasuda, Hisato Iwata, Shinsuke Tanabe, Haruo Takeshita
    ARCHIVES OF TOXICOLOGY 90 4 1009 - 1012 2016年04月 研究論文(学術雑誌) 
    The associations of four single nucleotide polymorphisms (p.Arg194Trp, p.Arg280His, p.Pro206Pro, and p.Arg399Gln) in X-ray repair cross-complementing group 1 with urinary arsenic metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated in a Vietnamese population (n = 100). Individuals with genotype AA in p.Pro206Pro showed significantly higher urinary monomethylarsonic acid (MMA(V)) and lower dimethylarsinic acid (DMA(V))/MMA(V) ratio than genotype AG. As for p.Arg399Gln, both Arg/Arg homozygous subjects and Arg/Gln heterozygous individuals showed a significantly higher urinary inorganic As percentage and lower 8-OHdG concentrations than Gln/Gln homozygous. Our results suggested that Arg399Gln is a functional SNP that may be related to DNA repair activity.
  • Hazuki Mizukawa, Kei Nomiyama, Susumu Nakatsu, Hisato Iwata, Jean Yoo, Akira Kubota, Miyuki Yamamoto, Mayumi Ishizuka, Yoshinori Ikenaka, Shouta M. M. Nakayama, Tatsuya Kunisue, Shinsuke Tanabe
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 50 1 444 - 452 2016年01月 研究論文(学術雑誌) 
    There are growing concerns about the increase in hyperthyroidism in pet cats due to exposure to organo-halogen contaminants and their hydroxylated metabolites. This study investigated the blood contaminants polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PCBs, OH-PBDEs, and MeO-PBDEs), in pet dogs and cats. We also measured the residue levels of these compounds in commercially available pet foods. Chemical analyses of PCBs and OH-PCBs showed that the OH-PCB levels were 1 to 2 orders of magnitude lower in cat and dog food products than in their blood, suggesting that the origin of OH-PCBs in pet dogs and cats is PCBs ingested with their food. The major congeners of OH-/MeO-PBDEs identified in both pet food products and blood were natural products (60H-/MeO-BDE47 and 2'OH-/MeO-BDE68) from marine organisms. In particular, higher concentrations of 60H-BDE47 than 2'OH-BDE68 and two MeO-PBDE congeners were observed in the cat blood, although MeO-BDEs were dominant in cat foods, suggesting the efficient biotransformation of 60H-BDE47 from 6MeO-BDE47 in cats. We performed in vitro demethylation experiments to confirm the biotransformation of MeO-PBDEs to OH-PBDEs using liver microsomes. The results showed that 6MeO-BDE47 and 2'MeO-BDE68 were demethylated to 60H-BDE47 and 2'OH-BDE68 in both animals, whereas no hydroxylated metabolite from BDE47 was detected. The present study suggests that pet cats are exposed to MeO-PBDEs through cat food products containing fish flavors and that the OH-PBDEs in cat blood are derived from the CYP-dependent demethylation of naturally occurring MeO-PBDE congeners, not from the hydroxylation of PBDEs.
  • Jean Yoo, Masashi Hirano, Hazuki Mizukawa, Kei Nomiyama, Tetsuro Agusa, Eun-Young Kim, Shinsuke Tanabe, Hisato Iwata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 49 24 14588 - 14596 2015年12月 研究論文(学術雑誌) 
    The aim of this study was to understand the cytochrome P450 (CYP)-dependent metabolic pathway and potency of polychlorinated biphenyls (PCBs) in the Baikal seal (Pusa sibirica). In vitro metabolism of 62 PCB congener mixtures was investigated by using liver microsomes of this species. A decreased ratio of over 20% was observed for CB3, CB4, CB8, CB15, CB19, CB22, CB37, CB54, CB77, and CB105, suggesting the preferential metabolism of low-chlorinated PCBs by CYPs. The highly activated metabolic pathways in Baikal seals that were predicted from the decreased PCBs and detected hydroxylated PCBs (OH-PCBs) were CB22 to 4'OH-CB20 and CB77 to 4'OH-CB79. The total amount of OH-PCBs detected as identified and unidentified congeners accounted for only a 3.8 +/- 1.7 mol % of loaded PCBs, indicating many unknown PCB metabolic pathways. To explore factors involved in CYP-dependent PCB metabolism, we examined the relationships among the structural and physicochemical properties of PCBs, the in silica PCB-CYP docking parameters, and the in vitro PCB decreased ratios by principal component analysis. Statistical analysis showed that the decreased PCB ratio was at least partly accounted for by the substituted chlorine number of PCBs and the distance from the CI-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and 2B.
  • See-Wun Cho, Ken-ichi Suzuki, Yoshiaki Miura, Tatsuhiko Miyazaki, Masato Nose, Hisato Iwata, Eun-Young Kim
    ARCHIVES OF TOXICOLOGY 89 11 2027 - 2038 2015年11月 研究論文(学術雑誌) 
    The aryl hydrocarbon receptor (AHR) is responsible for susceptibility to its ligand-dependent responses. However, the effect of non-AHR factors is less clear. To explore the non-AHR factors, we used two mouse strains with different AHR genetic variants, namely C3H/lpr and MRL/lpr strains with Ala and Val as the 375th amino acid residue, respectively. To assess the contribution of AHR alone, COS-7 cells transiently expressing AHR from each strain were treated with 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and xenobiotic-responsive element (XRE)-driven reporter gene activities were measured. FICZ-EC50 values for the C3H/lpr and MRL/lpr AHR-mediated transactivation were 0.023 and 0.046 nM, respectively, indicating a similar susceptibility in both AHR genotypes. In contrast, C3H/lpr AHR was fourfold more sensitive to TCDD than MRL/lpr AHR. By a pull-down assay using a XRE-containing PCR product as bait and the hepatic nuclear extracts of both FICZ-treated mouse strains, we identified two interacting proteins as heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2) and its splicing variant (hnRNP-A2b). Immunoprecipitation assays demonstrated the AHR interaction with hnRNP-A2/B1. When hnRNP-A2 was co-expressed with the MRL/lpr or C3H/lpr AHR in COS-7, FICZ treatment decreased EC50 to about threefold in both AHR genotypes, compared with EC50 in AHR alone. Similarly, hnRNP-A2b co-expression also lowered the FICZ-EC50 values. In TCDD-treated COS-7, responses depended on the AHR genotype; while no change in TCDD-EC50 was observed for C3H/lpr AHR when hnRNP-A2 was co-expressed, the value was reduced to nearly tenfold for MRL/lpr AHR. Co-transfection with hnRNP-A2b attenuated the AHR sensitivity to TCDD. In conclusion, the hnRNP-A2/B1 interacting with AHR may be a modulator of the AHR ligand sensitivity.
  • Hazuki Mizukawa, Kei Nomiyama, Tatsuya Kunisue, Michio X. Watanabe, Annamalai Subramanian, Hisato Iwata, Mayumi Ishizuka, Shinsuke Tanabe
    ENVIRONMENTAL RESEARCH 138 255 - 263 2015年04月 研究論文(学術雑誌) 
    The concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and their hydroxylated metabolites (OH-PCBs and OH-PBDEs) were measured in the blood of Eurasian wild pigs (Sus scrofa) from a municipal waste open dumping site (DS) and a reference site (RS) in South India. We showed that contamination with OH-PCBs was higher in female pigs from the DS than in all other adult pigs. The highest OH-PCB concentrations were found in piglets from the DS. Moreover, the hepatic expression levels of CYP1A and CYP2B were higher in piglets than in their dam, implying metabolism of PCBs by cytochrome P450 (CYP) enzymes. The OH-PCB congener profiles differed according to sex and collection sites, possibly because of variations in the expression levels of phase I and phase II enzymes among individual pigs, differences in the exposure sources, and maternal transfer of parent PCBs. The hepatic CYP1A expression levels were positively correlated with the blood concentrations of 4OH-CB107, 4OH-CB162, and 4OH-CB187, implying CYP1A-dependent formation of these OH-PCBs in the pig liver. We found no significant correlations between the blood concentrations of OH-PCBs and thyroid hormones (THs); however, the thyroxin (T-4) levels were lower in pigs from the DS than in pigs from the RS. Our limited dataset suggest that induced CYP enzymes accelerate the metabolism of xenobiotics and endogenous molecules in pigs. Thus, besides parental compounds, the risk of hydroxylated metabolites entering wildlife and humans living in and around municipal open waste dumping sites should be considered. (C) 2015 Elsevier Inc. All rights reserved.
  • Masashi Hirano, Ji-Hee Hwang, Hae-Jeong Park, Su-Min Bak, Hisato Iwata, Eun-Young Kim
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 49 6 3795 - 3804 2015年03月 研究論文(学術雑誌) 
    The aryl hydrocarbon receptor (AHR) mediates toxic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxin-like cornpounds (DLCs). Avian species possess multiple AHR isoforms (AHR1, AHR1,6, and AHR2) that exhibit species- and isoform-specific responses to ligands. To account for the ligand preference in terms of the structural features of avian AHRs, we generated in silico homology models of the ligand-binding domain of avian AHRs based on ho/o human HIF-2 alpha (PDB entry 3H7VV). Molecular docking simulations of TCDD and other DLCs with avian AHRls and AHR2s using ASEDock indicated that the interaction energy increased with the number of substituted chlorine atoms in congeners, supporting AHR transactivation potencies and World Health Organization TCDD toxic equivalency factors of congeners. The potential interaction energies of an endogenous AHR ligand, 6-formylindolo [3,2-b] carbazole (FICZ) to avian AHRs were lower than those of TCDD, which was supported by a greater potency of FICZ for in vitro AHR-mediated transactivation than TCDD. The molecular dynamics simulation revealed that mean square displacements in Ile324 and Ser380 of TCDD-bound AHR1 of the chicken, the most sensitive species to TCDD, were smaller than those in other avian AHR1s, suggesting that the dynamic stability of these amino acid residues contribute to TCDD preference. For avian AHR2, the corresponding residues (Val/Ser or Val/Ala type) were not responsible for differential TCDD sensitivity. Application of the three-dimensional reference interaction site model showed that the stabilization of TCDD binding to avian AHRs may be due to the solvation effect depending on the characteristics of two amino acids corresponding to Ile324 and Ser380 in chicken AHR1. This study demonstrates that in silica simulations of AHRs and ligands could be used to predict isoform-, ligand-, and species-specific interactions.
  • 阿草哲郎, 國頭 恭, N.M. Tue, V.T.M. Lan, T.B. Minh, P.T.K. Trang, 藤原純子, 竹下治男, 高橋 真, P.H. Viet, 田辺信介, 岩田久人
    日衛誌 70 3 186-196  2015年 [査読有り]
  • Tetsuro Agusa, Takashi Kunito, Nguyen Minh Tue, Vi Thi Mai Lan, Tu Binh Minh, Pham Thi Kim Trang, Junko Fujihara, Haruo Takeshita, Shin Takahashi, Pham Hung Viet, Shinsuke Tanabe, Hisato Iwata
    Nihon eiseigaku zasshi. Japanese journal of hygiene 70 186 - 196 2015年01月 
    Arsenic metabolism affects the susceptibility of humans to arsenic toxicity; therefore, clarification of the factors associated with individual variations in arsenic metabolism is an important task. Genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in arsenic (+3 oxidation state) methyltransferase (AS3MT), which can methylate arsenic compounds using S-adenosyl-l-methionine (AdoMet), have been reported to modify arsenic methylation. In this review, we summarize studies conducted by us in Vietnam and by others on the association of AS3MT genetic polymorphisms with arsenic metabolism as well as human health effects. Most of the SNPs in AS3MT showed inconsistent results in terms of genotype-dependent differences in arsenic metabolism among the studies. However, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the study population: AS3MT 12390 (rs3740393) affected the second step of methylation of arsenic, whereas 14458 (rs11191439) affected the first methylation step.
  • Mikiko Soejima, Tetsuro Agusa, Hisato Iwata, Junko Fujihara, Takashi Kunito, Haruo Takeshita, Vi Thi Mai Lan, Tu Binh Minh, Shin Takahashi, Pham Thi Kim Trang, Pham Hung Viet, Shinsuke Tanabe, Yoshiro Koda
    LEGAL MEDICINE 17 1 14 - 16 2015年01月 研究論文(学術雑誌) 
    The haptoglobin (HP) gene deletion allele (HPdel) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HPdel in addition to the distribution of common HP genotypes in 293 Vietnamese. The HPdel was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
  • Iwata, Hisato, Yamaguchi, Keisuke, Takeshita, Yoko, Kubota, Akira, Hirakawa, Shusaku, Isobe, Tomohiko, Hirano, Masashi, Kim, Eun-Young
    Aquatic Toxicology 162 138 - 151 2015年 研究論文(学術雑誌) 
    © 2015 Elsevier B.V. This study aimed to elucidate the catalytic function of cytochrome P450 (CYP) 1 enzymes in aquatic mammals. Alkoxyresorufin O-dealkylation (AROD) activities including methoxy- (MROD), ethoxy- (EROD), pentoxy- (PROD), and benzyloxyresorufin O-dealkylation (BROD), and 2- and 4-hydroxylation activities of 17β-estradiol (E2) were measured by using yeast-expressed Baikal seal (Pusa sibirica) CYP1A1, 1A2, and 1B1 proteins. Heterologous protein expression of the Baikal seal CYP1s (bsCYP1s) in yeast microsomes was confirmed by reduced CO-difference spectra and immunoblotting. Heterologously expressed human CYP1 enzyme (hCYP1) activities were simultaneously measured and compared with those of bsCYP1 isozymes. Recombinant bsCYP1A1 protein showed the highest Vmaxof EROD, followed by MROD, PROD, and BROD, similar to that of hCYP1A1. Vmax/Kmratios of all AROD activities catalyzed by bsCYP1A1 were lower than those catalyzed by hCYP1A1, suggesting less potential for AROD by bsCYP1A1. Enzymatic assays for bsCYP1A2 showed no or minimal AROD activities, while hCYP1A2 displayed MROD and EROD activities. bsCYP1B1 showed an AROD profile (EROD>BROD>MROD»PROD) similar to that of hCYP1B1; however, Vmax/Kmratios of all AROD activities by bsCYP1B1 were higher. Yeast microsomes containing bsCYP1A1 and 1B1 and hCYP1A1, 1A2, and 1B1 metabolized E2to 2-OHE2and 4-OHE2, whereas bsCYP1A2 showed no such activity. Comparison of 4- and 2-hydroxylations of E2by CYP1As suggests that bsCYP1A1, hCYP1A1, and 1A2 preferentially catalyze 2- rather than 4-hydroxylation. As for CYP1B1, the Vmax/Kmratios suggest that both Baikal seal and human CYPs catalyze 4- rather than 2-hydroxylation. Interspecies comparison showed that bsCYP1B1 has higher metabolic potencies for both E2hydroxylations than does hCYP1B1, whereas the activity of bsCYP1A1 was lower than that of hCYP1A1. Messenger RNA expression levels of bsCYP1s in the liver of Baikal seals indicated that bsCYP1A1 and 1A2 enzymes contributed to 16.2% and 83.7% of total CYP1s, respectively; bsCYP1B1 accounted for only 0.06%. Addition of anti-human CYP1A1 antibody in seal liver microsomes suppressed EROD activity more than did anti-human CYP1A2 antibody. Therefore, EROD may be catalyzed by hepatic bsCYP1A1 but not bsCYP1A2, consistent with the results of yeast-expressed bsCYP1A1 and 1A2. In silico substrate-docking models of bsCYP1s suggested that the defect in bsCYP1A2 enzymatic activities may be accounted for by the Pro substitution of highly conserved Thr in the I-helix, which is involved in formation of a hydrogen bond with the hydroperoxy intermediate on the heme. This Thr-Pro substitution is evolutionarily conserved across aquatic mammals and could explain their lower metabolic potential for persistent organic pollutants.
  • Daisuke Imaeda, Kei Nomiyama, Tatsuya Kunisue, Hisato Iwata, Oyuna Tsydenova, Masao Amano, Evgeny A. Petrov, Valeriy B. Batoev, Shinsuke Tanabe
    CHEMOSPHERE 114 1 - 8 2014年11月 研究論文(学術雑誌) 
    We have previously demonstrated that Baikal seals (Pusa sibirica) are still being exposed to polychlorinated biphenyls (PCBs), and the population is at risk. In the present study, we measured the residue levels of PCBs and their hydroxylated metabolites (OH-PCBs) in the blood of Baikal seals and assessed the impact of OH-PCBs on the thyroid function. Blood concentrations of PCBs and OH-PCBs were in the range of 2.8130 ng g(-1) wet wt. and 0.71-4.6 ng g(-1) wet wt., respectively. Concentrations of higher-chlorinated OH-PCBs (hexa- to octa-PCBs) were more than 70% to total OH-PCB concentrations, indicating Baikal seals are mostly risked by higher-chlorinated OH-PCBs. High levels of 4OH-CB146 and 4OH-CB187 and low levels of 4OH-CB107/4'OH-CB108 found in Baikal seals were different from those in other phocidae species, suggesting the unique drug-metabolizing enzyme activities and/or contamination sources in this species. Concentrations of some OH-PCBs in males were significantly higher than those in females. These results suggest that these isomers may be preferentially transferred from mother to pup via cord blood. However, concentrations of almost all the isomers were not significantly correlated with the levels of blood total T3 and T4, implying less impact of PCB-related compounds on the thyroid hormone circulation. (C) 2014 Elsevier Ltd. All rights reserved.
  • Kei Nomiyama, Shusaku Hirakawa, Akifumi Eguch, Chika Kanbara, Daisuke Imaeda, Jean Yoo, Tatsuya Kunisue, Eun-Young Kim, Hisato Iwata, Shinsuke Tanabe
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 48 22 13530 - 13539 2014年11月 研究論文(学術雑誌) 
    We have previously reported that high accumulation of dioxins and related compounds induced cytochrome P450 (CYP 1s) isozymes in the liver of wild Baikal seals, implying the enhanced hydroxylation of polychlorinated biphenyls (PCBs). The present study attempted to elucidate the residue concentrations and patterns of PCBs and hydroxylated PCBs (OH-PCBs) in the livers of Baikal seals. The hepatic residue concentrations were used to assess the potential effects of PCBs and OH-PCBs in combination with the analyses of serum thyroid hormones, hepatic mRNA levels, and biochemical markers. The hepatic expression levels of CYP1 genes were positively correlated with the concentration of each OH-PCB congener. This suggests chronic induction of these CYP1 isozymes by exposure to PCBs and hydroxylation of PCBs induced by CYP 1s. Hepatic mRNA expression monitoring using a custom microarray showed that chronic exposure to PCBs and their metabolites alters the gene expression levels related to oxidative stress, iron ion homeostasis, and inflammatory responses. In addition, the concentrations of OH-PCBs were negatively correlated with l-thyroxine (T-4) levels and the ratios of 3,3',5-triiodo-l-thyronine (T-3)/reverse 3,3',5'-triiodo-l-thyroninee (rT(3)). These observations imply that Baikal seals contaminated with high levels of OH-PCBs may undergo the disruption of mechanisms related to the formation (or metabolism) of T-3 and T-4 in the liver.
  • Satoko Niimi, Mai Imoto, Tatsuya Kunisue, Michio X. Watanabe, Eun-Young Kim, Kei Nakayama, Genta Yasunaga, Yoshihiro Fujise, Shinsuke Tanabe, Hisato Iwata
    ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 108 95 - 105 2014年10月 研究論文(学術雑誌) 
    Hepatic concentrations of persistent organochlorines (OCs) were determined in the common minke whale (Balaenoptera acutorostrata) from the North Pacific. To investigate the effects of OCs on the transcriptome in the minke whale, the present study constructed a hepatic oligo array of this species where 985 unique oligonucleotides were spotted and further analyzed the relationship between the OC levels and gene expression profiles of liver tissues. The stepwise multiple linear regression analysis identified 32 genes that correlated with hepatic OC levels. The mRNA expression levels of seven cytochrome P450 (CYP) genes, CYP1A1, 1A2, 208, 2E1, 3A72, 4A35, and 4V6 showed no clear correlations with the concentration of each OC, suggesting that the accumulated OCs in the liver did not reach levels that could alter CYP expression. Among the genes screened by the custom oligo array analysis, hepatic mRNA expression levels of 16 genes were further measured using quantitative real-time reverse transcription polymerase chain reaction. The mRNA levels of vitamin D-binding protein (DBP) were negatively correlated with non-ortho coplanar polychlorinated biphenyl (PCB) levels. Androgen receptor-associated coregulator 70 (ARA70) expression levels showed a significant positive correlation with concentrations of non-ortho coplanar PCB169. These correlations suggest that coplanar PCB-reduced DBP expression could suppress vitamin D receptor-mediated signaling cascades in peripheral tissues. Alternatively, the suppression of vitamin D receptor signaling cascade could be enhanced through competition with the androgen receptor signaling pathway for ARA70. In addition, a negative correlation between kynureninase and PCB169 levels was also observed, which suggest an enhanced accumulation of an endogenous aryl hydrocarbon receptor agonist, kynurenine in the minke whale population. Further studies are necessary to translate the changes in the transcriptome to toxicological outcomes including the disruption of the nervous and immune systems. (C) 2014 Elsevier Inc. All rights reserved.
  • Midori Iida, Su-Min Bak, Yasunori Murakami, Eun-Young Kim, Hisato Iwata
    AQUATIC TOXICOLOGY 154 39 - 47 2014年09月 研究論文(学術雑誌) 
    The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is mainly mediated by an aryl hydrocarbon receptor (AHR), which regulates the transcription of multiple target genes including cytochrome P450 1A (CYP1A). Our pervious study identified the presence of TCDD-induced defects of peripheral nerve projection in red seabream (Pagrus major) embryos. However, it remains unclear whether the TCDD-induced peripheral neurotoxicity is mediated by the AHR. To assess the contribution of the red seabream AHR (rsAHR) signaling pathway to the neuronal toxicity, red seabream embryos at 10 h post-fertilization (hpf) were treated for 80 min with TCDD (0, 0.3, 5.3, and 37 nM in seawater) alone or in combination with CH223191 (500 nM in seawater), which is an AHR antagonist. A preliminary in vitro reporter gene assay confirmed that TCDD-induced transcriptional activity via rsAHR1 and rsAHR2 was suppressed by CH223191 treatment in a dose-dependent manner. CYP1A mRNA expression in embryos was determined by 2-step real time quantitative-polymerase chain reaction at 24 and 120 hpf and in situ hybridization at 48, 72, 96 and 120 hpf. The morphology of the peripheral nerve system (PNS) was also microscopically observed by fluorescent staining using an anti-acetylated tubulin antibody at 120 hpf. CYP1A mRNA expression was dose-dependently induced by TCDD at all of the examined developing stages. The suppression of TCDD-induced CYP1A expression by CH223191 treatment was observed in embryos at 24 and 48 hpf, while the effect of the rsAHR antagonist disappeared at 96 and 120 hpf. This phenomenon indicated the transient suppression of TCDD-induced rsAHR activation by CH223191 treatment. The immunostaining of peripheral nerves at 120 hpf demonstrated that the projections of the craniofacial nerve were altered in TCDD-treated embryos, and the frequency of TCDD-induced abnormal projections was not prevented by co-treatment with CH223191. These results indicate that the transient suppression of TCDD-induced rsAHR activation during the early developing stages of the red seabream does not influence the abnormal projection of peripheral nerves. In conclusion, transient rsAHR activation in the early stages of development is not involved in the neurotoxicity. (C) 2014 Elsevier B.V. All rights reserved.
  • RNA-seq analysis of the mysid crustacean transcriptome following exposure to naturally occurring 1,3,7-Tribromodibenzo-p-dioxin
    Hirano M, Uchida M, Kusano T, Arizono K, Iwata H
    Organohalogen Compounds 76 981 - 984 2014年08月 [査読有り]
  • Jin Seon Lee, Kohei Iwabuchi, Koji Nomaru, Nobumasa Nagahama, Eun Young Kim, Hisato Iwata
    Toxicological Sciences 136 2 450 - 466 2013年12月 研究論文(学術雑誌) 
    Dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause toxic effects through activation of the aryl hydrocarbon receptor (AHR)-mediated signaling pathway. Our previous studies have investigated the function of 2 AHR isoforms (AHR1 and AHR2) in avian species and identified a third AHR in the chicken (Gallus gallus) genome. Knowledge of multiple avian AHRs is indispensable to understand molecular mechanisms of AHRmediated toxic effects and establish risk assessment framework for environmental AHR ligands in avian species. In this study, we successfully isolated a third novel AHR1-like cDNA from chicken and designated it as chicken AHR1 beta (ckAHR1β). The mRNA expression of ckAHR1β was primarily detected in the liver, and the hepatic protein expression was confirmed by Western blotting. Although mRNA expression of ckAHR1β was not altered by in ovo TCDD exposure, ckAHR1β exhibited specific binding to [3H] TCDD, TCDD-dependent nuclear translocation, and interaction with xenobiotic responsive elements (XREs) and AHR nuclear translocators (ARNTs). In vitro XRE-driven reporter gene assays revealed ckAHR1β-mediated transactivation of TCDD in a dosedependent manner, showing a 10-fold reduced sensitivity (high EC50) compared with that mediated by ckAHR1. The mutation of Val371 to Ser371 in the ligand-binding domain of ckAHR1β shifted the TCDD-EC50 toward the value observed in ckAHR1, indicating the critical roles of the amino acid in sensitivity. Furthermore, ckAHR1β-mediated transactivation of TCDD was enhanced by 17β-estradiol (E2)-activated chicken estrogen receptor a (ckERa), suggesting a positive cross talk between ckERa and ckAHR1β signaling pathway. Both TCDD-induced and its enhanced activities by E2 were suppressed by the ckAHR repressor in a manner similar to ckAHR1. Collectively, our findings discover the role of ckAHR1β in dioxin toxicity and give an insight into the evolutionary history of the AHR signaling pathway. © The Author 2013. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
  • N. Fujisawa, W. S. Darwish, Y. Ikenaka, E. Kim, J. Lee, H. Iwata, S. Nakayama, M. Ishizuka
    POULTRY SCIENCE 92 7 1921 - 1929 2013年07月 研究論文(学術雑誌) 
    A 1,000-fold difference has been reported in dioxin sensitivity between avian species. This difference is because the 2 amino acids in the type 1 aryl hydrocarbon receptor (AhR1), at positions 325 and 381, correspond to Leu324 and Ser380 in chickens. The chicken had been reported to be the only avian species to possess a sensitive form of AhR1. This is the first study to reveal that the ostrich (Struthio camelus), a nonchicken species, also has a pair of amino acids (Ile-325 and Ser-381) that show high ligand affinity. However, the alignment of the AhR1 cDNA sequence showed that the AhR sequence in the ostrich was different than that of other avian species even though the critical amino acids were observed at positions 325 and 381. Ostrich AhR1 was also evaluated in a heterologous expression study. Ostrich AhR1 showed very high transcriptional activity of the cytochrome P450 1A5 (CYP1A5) gene in African Green Monkey Cercopithecus aethiops kidney cells (COS-7) treated with Sudan III. In primary cultures of ostrich kidney cells, CYP1A5 expression was induced by Sudan III at a lower (or almost identical) concentration to that observed in the chicken. The present study revealed a new AhR ligand sensitive avian species (i.e., the ostrich).
  • Leena Mol Thuruthippallil, Akira Kubota, Eun-Young Kim, Hisato Iwata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 47 12 6656 - 6663 2013年06月 研究論文(学術雑誌) 
    Our line of papers revealed that the common (great) cormorant (Phalacrocorax carbo) possesses two isoforms of the aryl hydrocarbon receptor (ccAHR1 and ccAHR2). This paper addresses in vitro tests of the ccAHR signaling pathways to solve two questions: (1) whether there are functional differences in the two ccAHR isoforms, and (2) whether a molecular perturbation, cytochrome P450 1A (ccCYP1A) induction, in the population-level can be predicted from the in vitro tests. The transactivation potencies mediated by ccAHR1 and ccAHR2 were measured in COS-7 cells treated with 15 selected dioxins and related compounds (DRCs), where ccAHR1 or ccAHR2 expression plasmid and ccCYP1A5 promoter/enhancer-linked luciferase reporter plasmid were transfected. For congeners that exhibited dose-dependent luciferase activities, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) relative potencies (REPs) and induction equivalency factors (IEFs) were estimated. ccAHR1-IEF profile was similar to WHO avian TCDD toxic equivalency factor (TEF) profile except for dioxin-like polychlorinated biphenyls that showed lower IEFs in ccAHR1-driven reporter assay. ccAHR2-IEF profile was different from WHO TEFs and ccAHR1-IEFs. Notably, 2,3,4,7,8-PeCDF was more potent than TCDD for ccAHR2-mediated response. Using ccAHR1- and ccAHR2-IEFs and hepatic DRC concentrations in the Lake Biwa cormorant population, total TCDD induction equivalents (IEQs) were calculated for each ccAHR-mediated response. Nonlinear regression analyses provided significant sigmoidal relationships of ccAHR1- and ccAHR2-derived IEQs with hepatic ccCYP1A5 mRNA levels, supporting the results of in vitro ccAHR-mediated TCDD dose-response curves. Collectively, our in vitro AHR reporter assay potentially could be an alternative to molecular epidemiology of the species of concern regarding CYP1A induction by AHR ligands.
  • Michio X. Watanabe, Tatsuya Kunisue, Norifumi Ueda, Masato Nose, Shinsuke Tanabe, Hisato Iwata
    ENVIRONMENT INTERNATIONAL 53 53 - 61 2013年03月 研究論文(学術雑誌) 
    Concentrations of persistent organochlorine compounds (OCs) including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in the liver and adipose tissue of Japanese cadavers were measured, and their toxicokinetics were examined in association with hepatic cytochrome P450 (CYP) 1A protein expression levels. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were 66 +/- 74 and 65 +/- 57 pg/g lipid weight (mean +/- S.D.) in the liver and adipose tissue, respectively. Total PCBs (sum of 62 congeners targeted), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) and beta-hexachlorocyclohexane (beta-HCH) were detected at concentrations over 1 mu g/g lipid in both tissues of some specimens. For most of the dioxin-like congeners, total PCBs, p,p'-DDE, oxychlordane, alpha- and beta-HCH, hexachlorobenzene (HCB), and tris(4-chlorophenyl)methane (TCPMe), age-dependent increases in concentrations were found in the adipose tissue of males. No such age-dependent trend was observed in the liver, suggesting that there are different mechanisms underlying the hepatic concentrations of OCs. Immunoblot analyses indicated detectable expression of hepatic CYP1A2 protein, whereas no CYP1A1 protein was detected. The CYP1A2 expression levels were positively correlated with concentrations (on wet weight basis) of 2,3,4,7,8-P5CDF, the dominant TEQ-contributed congeners in the liver, indicating the induction of this CYP. Hepatic CYP1A2 protein levels were strongly correlated with the liver to adipose concentration (L/A) ratios of PCDD/F congeners with more than 5 chlorine atoms. Together with higher concentrations of the congeners in the liver than in the adipose tissue, the observation on L/A ratios of highly chlorinated PCDD/Fs suggests that induced hepatic CYP1A2 protein is involved in their sequestration in this human population, as observed in model animals (rodents). Nonetheless, the magnitude of hepatic sequestration (L/A ratio) of PCDD/Fs in this human population was lower than in other mammals and birds, reported previously. This study emphasizes the fact that toxicokinetics of some OCs can be affected at least partly by CYP1A2 protein levels in humans. For the extrapolation of their toxicokinetics from model animals to humans, knowledge on the induction and sequestration potencies of CYP1A is necessary. (C) 2013 Elsevier Ltd. All rights reserved.
  • Midori Iida, Eun-Young Kim, Yasunori Murakami, Yasuhiro Shima, Hisato Iwata
    AQUATIC TOXICOLOGY 128 193 - 202 2013年03月 研究論文(学術雑誌) 
    We investigated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced effects on the morphology of peripheral nervous system (PNS) in the developing red seabream (Pagrus major) embryos. The embryos at 10 h post-fertilization (hpf) were treated with 0, 0.1, 0.4 or 1.7 mu g/L of TCDD in seawater for 80 min. The morphology of PNS was microscopically observed with florescence staining using an anti-acetylated tubulin antibody at 48, 78, 120 and 136 hpf. Axon length of facial nerve (VII) was found to be shortened by TCDD exposure. Axon guidance in the glossopharyngeal nerve (IX) and vagus nerve (X) was altered at 120 and 136 hpf in a TCDD dose-dependent manner. Lowest observable effect level of TCDD (0.1 mu g/L) that induced the morphological alteration of PNS was lower than those of other endpoints on morphological deformities so far reported. Given that the growth cone at the tip of growing nerve axons advances under the influence of its surrounding tissues, we hypothesized that TCDD exposure would affect (1) the nerve cell proliferation/differentiation, (2) the structure of muscle as an axon target and (3) the nerve guidance factor in the embryos. By the immunostaining of embryos with an antibody against the neuronal specific RNA-binding protein, HuD, and an antibody against the sarcomeric myosin, no morphological effects were observed on the neural proliferation/differentiation and the structure of facial muscles of TCDD-treated embryos. In contrast, whole mount in situ hybridization of semaphorin 3A (Sema3A), a secretory axon repulsion factor, revealed the altered expression pattern of its transcripts in TCDD-treated embryos. Our findings suggest that TCDD treatment affects the projection of PNS in the developing red seabream embryos through the effects on the axonal growth cone guidance molecule such as Sema3A, but not On the neuronal differentiation/proliferation and axon target. The PNS in developing embryos may be one of the most sensitive biomarkers to the exposure of dioxin-like compounds. (c) 2012 Elsevier B.V. All rights reserved.
  • Su-Min Bak, Midori Iida, Masashi Hirano, Hisato Iwata, Eun-Young Kim
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 47 6 2877 - 2885 2013年03月 研究論文(学術雑誌) 
    To evaluate species- and isoform-specific responses to dioxins and related compounds (DRCs) via aryl hydrocarbon receptor (AHR) in the red seabream (Pagrus major), we constructed a reporter gene assay system. Each expression plasmid of red seabream AHR1 (rsAHR1) and AHR2 (rsAHR2) together with a reporter plasmid containing red seabream CYP1A 5'-flanking region were transfected into COS-7 cells. The cells were treated with graded concentrations of seven DRC congeners including 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, I,2,3,4,7,8-HxCDD, 2,3,7,8-TCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, and PCB126. Both rsAHR1 and rsAHR2 exhibited dose-dependent responses for all the tested congeners. The rsAHR isoform-specific TCDD induction equivalency factors (rsAHR1- and rsAHR2-IEFs) were calculated on the basis of 2,3,7,8-TCDD relative potency derived from the dose response of each congener. The rsAHR1-IEFs of PeCDD, HxCDD, TCDF, PeCDF, and HxCDF were estimated as 0.17, 0.29, 2.5, 1.5, and 0.27, respectively. For PCB126, no rsAHR1-IEF was given because of less than 10% 2,3,7,8-TCDD maximum response. The rsAHR2-IEFs of PeCDD, HxCDD, TCDF, PeCDF, HxCDF, and PCB 126 were estimated as 0.38, 0.13, 1.5, 0.93, 0.20, and 0.0085, respectively. The rsAHR1/2-IEF profiles were different from WHO toxic equivalency factors for fish. In silico docking simulations supported that both rsAHRs have potentials to bind to these congeners. These results suggest that dioxin toxicities may be mediated by both rsAHRs in red seabreams.
  • Pham Thi Dau, Hiroki Sakai, Masashi Hirano, Hiroshi Ishibashi, Yuki Tanaka, Kenji Kameda, Takahiro Fujino, Eun-Young Kim, Hisato Iwata
    TOXICOLOGICAL SCIENCES 131 1 116 - 127 2013年01月 研究論文(学術雑誌) 
    The constitutive androstane receptor (CAR) not only displays a high basal transcriptional activity but also acts as a ligand-dependent transcriptional factor. It is known that CAR exhibits different ligand profiles across species. However, the mechanisms underlying CAR activation by chemicals and the species-specific responses are not fully understood. The objectives of this study are to establish a high-throughput tool to screen CAR ligands and to clarify how CAR proteins from the Baikal seal (bsCAR) and the mouse (mCAR) interact with chemicals and steroid receptor coactivator 1 (SRC1). We developed the surface plasmon resonance (SPR) system to assess quantitatively the interaction of CAR with potential ligands and SRC1. The ligand-binding domain (LBD) of bsCAR and mCAR was synthesized in a wheat germ cellfree system. The purified CAR LBD was then immobilized on the sensor chip for the SPR assay, and the kinetics of direct interaction of CARs with ligand candidates was measured. Androstanol and androstenol, estrone, 17-estradiol, TCPOBOP, and CITCO showed compound-specific but similar affinities for both CARs. The CAR-SRC1 interaction was ligand dependent but exhibited a different ligand profile between the seal and the mouse. The results of SRC1 interaction assay accounted for those of our previous in vitro CAR-mediated transactivation assay. In silico analyses also supported the results of CAR-SRC1 interaction; there is little structural difference in the ligand-binding pocket of bsCAR and mCAR, but there is a distinct discrimination in the helix 11 and 12 of these receptors, suggesting that the interaction of ligand-bound CAR and SRC1 is critical for determining species-specific and ligand-dependent transactivation over the basal activity. The SPR assays demonstrated a potential as a high-throughput screening tool of CAR ligands.
  • Akira Kubota, Kumiko Yoneda, Shinsuke Tanabe, Hisato Iwata
    Environmental Pollution 178 300 - 305 2013年 研究論文(学術雑誌) 
    This study focuses on gender-specific accumulation features of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in common (great) cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan. Male cormorants showed a tendency to have higher levels of PCDD/DFs and DL-PCBs than did females. For PCDDs, the male-to-female concentration ratio (M/F ratio) for each congener significantly decreased with the liver-to-muscle concentration ratio (Li/Mu ratio). For PCDFs, there also was a weak negative relationship between Li/Mu ratio and M/F ratio. In contrast, for DL-PCBs, M/F ratios showed no correlation with Li/Mu ratios, but increased with an increase in lipophilicity. These results, together with observations from prior studies, suggest that congener-specific hepatic sequestration may be a factor limiting the maternal transfer of PCDDs and, to a lesser extent, PCDFs. Maternal transfer of DL-PCBs seems to favor more lipophilic congeners in the cormorants. © 2013 Elsevier B.V. All rights reserved.
  • Akira Kubota, Michio X. Watanabe, Eun-Young Kim, Kumiko Yoneda, Shinsuke Tanabe, Hisato Iwata
    ENVIRONMENTAL POLLUTION 168 131 - 137 2012年09月 研究論文(学術雑誌) 
    To validate the outcome of the national regulation on dioxins emission implemented in 1999, this study investigated temporal trends of chlorinated dioxins and related compounds (DRCs) in liver of common cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan between 2001 and 2008, as a part of the "Survey on the State of Dioxins Accumulation in Wildlife" conducted by the Ministry of the Environment, Japan. We also measured a biomarker of DRCs exposure, the cytochrome P450 1A (CYP1A)-dependent O-dealkylation activity of alkoxyresorufins (AROD), including methoxy-, ethoxy-, pentoxy- and benzyloxy-resorufins in the samples over 2001-2007. Neither TEQ nor AROD activity showed any clear declining trend over the time period, although the emission of DRCs during the corresponding period was estimated to be apparently decreasing. Our data indicate that the concentration of recalcitrant DRCs in the cormorant during 2001-2008 was scarcely affected by the national regulation on dioxins emission. (c) 2012 Elsevier Ltd. All rights reserved.
  • Mikiko Soejima, Ryo Fujimoto, Tetsuro Agusa, Hisato Iwata, Junko Fujihara, Haruo Takeshita, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, Tamiko Nakajima, Joji Yoshimoto, Shinsuke Tanabe, Yoshiro Koda
    TRANSFUSION 52 6 1268 - 1275 2012年06月 研究論文(学術雑誌) 
    BACKGROUND: The human FUT2 gene encodes a secretor-type a(1,2)fucosyltransferase, and many population-specific polymorphisms have been reported in the coding region. STUDY DESIGN AND METHODS: Direct sequencing, real-time polymerase chain reaction, and high-resolution melt (HRM) analysis were done to detect single-nucleotide polymorphism (SNPs) and copy number variations (CNVs) in a Vietnamese population. The impacts of two novel mutations on the encoded enzyme were examined by a transient expression study. RESULTS: The major nonfunctional allele in the 294 Vietnamese was se357,385, whereas no CNV was detected. Two novel SNPs, 818C>A (Thr273Asn) and 853G>A (Ala285Thr), distributed at low frequency, were shown to remarkably affect the enzyme activity. CONCLUSION: The allelic polymorphism of FUT2 in Vietnamese is similar to that of other East and Southeast Asian populations. This result may reflect the history and gene flow of this population. In addition, HRM analysis seems to be a simple and effective method for screening rare SNPs of FUT2 in a large number of samples. [Correction statement added after online publication 21-Dec-2011: Thr273Ala has been updated to Thr273Asn throughout.]
  • Nozomi Fujisawa, Yoshinori Ikenaka, Eun-Young Kim, Jin-Seon Lee, Hisato Iwata, Mayumi Ishizuka
    EUROPEAN JOURNAL OF WILDLIFE RESEARCH 58 1 167 - 175 2012年02月 研究論文(学術雑誌) 
    Some wild populations of fish-eating birds and raptors are exposed to high concentrations of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) and related compounds such as other 2,3,7,8-substituted polychlorinated dibenzop- dioxins and polychlorinated dibenzofurans and coplanar polychlorinated biphenyls, resulting in accumulation in their tissues. It has been demonstrated that TCDD-like chemicals cause toxic effects via aryl hydrocarbon receptor (AHR)-mediated signaling pathways. The aim of this study was to characterize the AHR from the peregrine falcon (Falco peregrines) to predict its sensitivity to TCDD-like chemicals. The AHR1, AHR2, and AHR nuclear translocator 1 of the peregrine falcon are more similar in amino acid sequence to avian species less sensitive to TCDD-like chemicals such as the cormorant (95%) than to more sensitive species such as the chicken (90%). From the amino acid sequence, it is likely that the ligand-binding affinity of peregrine falcon AHR1 and AHR2 would be very low compared with the chicken or other sensitive species, and it was actually proved by an in vitro reporter gene assay. We concluded that the peregrine falcon, one of raptor species, may be relatively resistant to TCDD-like chemicals.
  • Tetsuro Agusa, Takashi Kunito, Nguyen Minh Tue, Vi Thi Mai Lan, Junko Fujihara, Haruo Takeshita, Tu Binh Minh, Pham Thi Kim Trang, Shin Takahashi, Pham Hung Viet, Shinsuke Tanabe, Hisato Iwata
    METALLOMICS 4 1 91 - 100 2012年 研究論文(学術雑誌) 
    We investigated the association of As exposure and genetic polymorphism in glutathione S-transferase pi 1 (GSTP1) with As metabolism in 190 local residents from the As contaminated groundwater areas in the Red River Delta, Vietnam. Total As concentrations in groundwater ranged from <0.1 to 502 mu g l(-1). Concentrations of dimethylarsinic acid (DMA(V)), monomethylarsonic acid (MMA(V)), and arsenite (As(III)) in human urine were positively correlated with total As levels in the groundwater, suggesting that people in these areas may be exposed to As through the groundwater. The concentration ratios of urinary As(III) /arsenate (As(V)) and MMA(V) /inorganic As (IA; As(III) + As(V))(M/I), which are indicators of As metabolism, increased with the urinary As level. Concentration and proportion of As(III) were high in the wild type of GSTP1 Ile105Val compared with the hetero type, and these trends were more pronounced in the higher As exposure group (>56 mu g l(-1) creatinine in urine), but not in the lower exposure group. In the high As exposure group, As(III)/As(V) ratios in the urine of wild type of GSTP1 Ile105Val were significantly higher than those of the hetero type, while the opposite trend was observed for M/I. These results suggest that the excretion and metabolism of IA may depend on both the As exposure level and the GSTP1 Ile105Val genotype.
  • Hiroki Teraoka, Shino Ito, Haruki Ikeda, Akira Kubota, M. M. Abou Elmagd, Takio Kitazawa, Eun-Young Kim, Hisato Iwata, Daiji Endoh
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 46 1 27 - 33 2012年01月 研究論文(学術雑誌) 
    To assess possible impacts of environmental pollutants on gene expression profiles in a variety of organisms, we developed a novel differential display system with primer sets that are common in seven vertebrate species, based on degenerate oligonucleotide-primed PCR (DOP-PCR). An 8-mer inverse repeat motif was found in most transcripts from the seven vertebrates including fish to primates with detailed transcriptome information; more than 10 000 motifs were recognized in common in the transcripts of the seven species. Among them, we selected 275 common motifs that cover about 40-70% of transcripts throughout these species, and designed 275 DOP-PCR primers that were common to seven vertebrate species (common DOP-PCR primers). To detect genes responsive to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in developing embryos, differential display with common DOP-PCR primers was applied to embryonic liver of two avian species, the chicken (Gallus gallus) and the common cormorant (Phalacrocorax carbo), which were exposed in OVO to TCDD. The cDNA bands that showed differences between the control and TCDD-treated groups were sequenced and the mRNA expression levels were confirmed by real-time RT-PCR This approach succeeded in isolating novel dioxin-responsive genes that include 10 coding genes in the chicken, and 1 coding gene and 1 unknown transcript in the cormorant, together with cytochrome P450 1As that have, already been well established as dioxin markers. These results highlighted the usefulness of systematically designed novel differential display systems to search genes responsive to chemicals in vertebrates, including wild species, for which transcriptome information is not available.
  • Thuruthippallil Leena Mol, Eun-Young Kim, Hiroshi Ishibashi, Hisato Iwata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 46 1 525 - 533 2012年01月 研究論文(学術雑誌) 
    Our previous studies have detected high levels of dioxins and related compounds (DRCs) including polychlorinated dibenzo-p-dioxins (PCDDs), furans (PCDFs), and coplanar PCBs (Co-PCBs) in the black-footed albatross (BFA), Phoebastria nigripes, from the North Pacific region. We have also cloned two aryl hydrocarbon receptors, AHR1 and AHR2, of the BFA. To evaluate the sensitivity to DRCs in the BFA and to assess the stain the wild population, this study investigated the mRNA expression status of cytochrome P450 1A (CYP1A) induction levels of BFA AHR1 and AHR2 and also the transactivation potencies of each AHR by 15 selected DRC congeners. Quantitative real-time PCR of BFA AHR mRNAs showed that hepatic AHR1 is more highly expressed than AHR2. Transactivation by graded concentrations of individual DRCs was measured in COS-7 cells, where BFA AHR1 or AHR2 was transiently transfected. For congeners that exhibited AHR-mediated dose-dependent activities, 50% effective concentration (EC50) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) relative potencies (REPs) were estimated. Based on the estimates of the REPs, TCDD induction equivalency factors (IEFs) were determined. For BFA AHR1, PeCDF was equipotent to TCDD, but other congeners exhibited lower IEFs. For BFA AHR2, PCDD/F congeners except OCDD/F showed IEFs >= 1.0. Using BFA AHR1- or AHR2-IEFs and hepatic concentrations of DRCs in North Pacific BFAs, TCDD induction equivalents (IEQs) were calculated. We further constructed nonlinear regression models on the relationships between BFA AHR1- or AHR2-IEF derived total IEQ or WHO-TEF derived total TEQ and ethoxyresorufin-O-deethylase activity (EROD) in the liver of wild BFAs. The results indicated that the relationships of BFA AHR1- and AHR2-based IEQs and EROD were predictable from BFA AHR1- and AHR2-mediated transactivation by TCDD, respectively. Collectively, these results suggest that the in vitro assay incorporating the AHR of species of concern would be a useful tool to predict the sensitivity to DRCs in the species and CYP1A induction in the wild population.
  • Tatsuya Kunisue, Aldfumi Eguchi, Hisato Iwata, Shinsuke Tanabe, Kurunthachalam Kannan
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 45 23 10140 - 10147 2011年12月 研究論文(学術雑誌) 
    Thyroid hormones (THs) are essential for the regulation of growth and development in both humans and wildlife. Until recently, TH concentrations in the tissues of animals have been examined by immunoassay (IA) methods. IA methods are sensitive, but for TH analysis, they are compromised by a lack of adequate specificity. In this study, we determined the concentrations of six THs, L-thyroxine (T-4), 3,3',5-triiodo-L-thyronine (T-3), 3,3',5'-triiodo-L-thyronine (rT(3)), 3,5-diiodo-L-thyronine (3,5-T-2), 3,3'-diiodo-L-thyronine (3,3'-T-2), and 3-iodo-L-thyronine (3-T-1), in the serum of humans (n = 79) and wild Baikal seals (n = 37), by isotope ([C-13(6)]-T-4)dilution liquid chromatography (LC)-tandem mass spectrometry (MS/MS), and compared the TH levels with those measured by an electrochemiluminescent immunoassay (ECLIA) method. T-3 and T-4 were detected in all serum samples of both humans and Baikal seals, whereas T-1, 3,3'-T-2, and 3,5-T-2 were below the limit of detection (LOD). rT(3) was detected in Baikal seal sera at concentrations higher than T-3 in 28 seal samples, indicating an anomaly in deiodinase activity in Baikal seals. In humans, regression analyses of TH concentrations, measured by ECLIA and LC-MS/MS methods, showed significant correlations for T-4 (r = 0.852) and T-3 (r = 0.676; after removal of a serum sample with abnormal T-3 levels). In Baikal seals, a low correlation coefficient (r = 0.466) for T-4 levels and no correlation for T-3 levels (p = 0.093) were found between ECLIA and LC-MS/MS methods. These results suggest that interference by a nonspecific reaction against anti-T-3 and anti-T-4 antibodies used in the ECLIA can contribute to inaccuracies in TH measurement in Baikal seals. When the relationship between concentrations of THs in sera and dioxin-like toxic equivalents in blubber samples of Baikal seals (n = 19) was examined, a significantly negative correlation was found for serum T-4 levels measured by the LC-MS/MS method, but not for those measured by ECLIA. Thus, our results indicate that the LC-MS/MS method is more reliable and accurate for the elucidation of alteration in circulating TH levels in wildlife, as caused by environmental and physiological factors.
  • Junko Fujihara, Mikiko Soejima, Toshihiro Yasuda, Yoshiro Koda, Takashi Kunito, Hisato Iwata, Shinsuke Tanabe, Haruo Takeshita
    TOXICOLOGY AND APPLIED PHARMACOLOGY 256 2 174 - 178 2011年10月 研究論文(学術雑誌) 
    Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes in the base excision repair (BER) pathway influence the generation and repair of oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE 1) Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and Arg399Gln in the BER genes were analyzed, and the relationship between these 4 SNPs and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations of 100 Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1 326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did those with 326 Ser/Cys and Ser/Ser. As for APE1 sp148Glu, heterozygous subjects showed significantly higher urinary 8-OHdG concentrations than did those homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic frequencies of the 4SNP5 was performed in 10 population and previous reported data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations were higher than those in the African and Caucasian populations. As for APE1 Asp148Glu, Caucasians showed higher mutant frequencies than those shown by African and Asian populations. Among Asian populations, the Bangladeshi population showed relatively higher mutant allele frequencies of the APE1 Asp148Glu polymorphism. This study is the first to demonstrate the existence of genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1 Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes. Published by Elsevier Inc.
  • Shusaku Hirakawa, Daisuke Imaeda, Kei Nakayama, Masayuki Udaka, Eun-Young Kim, Tatsuya Kunisue, Masako Ogawa, Tomonari Matsuda, Saburo Matsui, Evgeny A. Petrov, Valeriy B. Batoev, Shinsuke Tanabe, Hisato Iwata
    AQUATIC TOXICOLOGY 105 1-2 89 - 99 2011年09月 研究論文(学術雑誌) 
    We have previously indicated that accumulation of chlorinated dioxins and related compounds (DRCs) induced cytochrome P450 (CYP) 1A1, 1A2 and 1B1 isozymes in the liver of wild Baikal seals (Pusa sibirica). Here we attempt to assess the potential effects of DRCs triggered by the induction of these CYP1 isozymes in this species, using an integrative approach, combining gene expression monitoring and biochemical assays. To screen genes that may potentially respond to the exposure of DRCs, we constructed a custom cDNA oligo array that can target mRNAs in Baikal seals, and monitored hepatic mRNA expression levels in the wild population. Correlation analyses between the hepatic total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) and mRNA levels supported our previous findings that high accumulation of DRCs induces the transcription of CYP1A1, CYP1A2 and CYP1B1 genes. In addition, our integrative assessment indicated that the chronic exposure to DRCs may alter the hepatic transcript levels of genes related to oxidative stress, Fe ion homeostasis, and inflammatory responses. The expression levels of CYP1A2 showed significant positive correlations with levels of malondialdehyde, a biomarker of lipid peroxidation, and of etheno-dA, a DNA adduct, suggesting that the lipid peroxidation may be enhanced through the production of reactive oxygen species (ROS) triggered by CYP1A2 induction. Moreover, there was a positive correlation between heme oxygenase activities and malondialdehyde levels, suggesting the prompted hems degradation by ROS. Fetuin-A levels, which are suppressed by inflammation, showed a significant negative correlation with TEQ levels, and hepcidin levels, which are conversely increased by inflammation, had significant positive correlations with malondialdehyde and etheno-dA levels, implying the progression of inflammation by DRC-induced oxidative stress. Taken together, we propose here that wild Baikal seals may suffer from effects of chronic exposure to DRCs on the induction of CYP1 isozymes, followed by increased oxidative stress, heme degradation and inflammation. (C) 2011 Elsevier B.V. All rights reserved.
  • Tetsuro Agusa, Shin-ya Yasugi, Asami Iida, Tokutaka Ikemoto, Yasumi Anan, Thijs Kuiken, Albert D. M. E. Osterhaus, Shinsuke Tanabe, Hisato Iwata
    MARINE POLLUTION BULLETIN 62 5 963 - 975 2011年05月 研究論文(学術雑誌) 
    Body distribution and growth- and nutritional status-dependent accumulation of 21 trace elements were investigated in harbor seals (Phoca vitulina) stranded in the North Sea coast in 2002. Higher concentrations and burdens of Mn, Se, Mo, Ag, Sn, Hg, and Bi in the liver, Cd in the kidney, As in the blubber, and Co, Sr, and Ba in the bone were observed. Significant positive correlations of hepatic Se, Mo, Ag, Cd, Sn, Hg, Tl, and Bi with standard body length were found, while significant negative relationships were detected for Mn, As, Rb, Sr, and Sb in the liver. Concentrations of Co, Se, Sr, Sn, Hg, and Bi in the liver, V. Sr, Ag, Sn, and Hg in the kidney, V. Mn, Co, Rb, Sr, Sn, Ba, and Pb in the blubber increased with decreasing blubber thickness of harbor seals, indicating enrichment of these elements in the target tissue by emaciation. (C) 2011 Elsevier Ltd. All rights reserved.
  • Akira Kubota, John J. Stegeman, Jared V. Goldstone, David R. Nelson, Eun-Young Kim, Shinsuke Tanabe, Hisato Iwata
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 153 3 280 - 289 2011年04月 研究論文(学術雑誌) 
    Cytochrome P450 CYP2 family enzymes are important in a variety of physiological and toxicological processes. CYP2 genes are highly diverse and orthologous relationships remain clouded among CYP2s in different taxa. Sequence and expression analyses of CYP2 genes in diapsids including birds and reptiles may improve understanding of this CYP family. We sought CYP2 genes in a liver cDNA library of the common cormorant (Phalacrocorax carbo), and in the genomes of other diapsids, chicken (Gallus gallus), zebra finch (Taeniopygia guttata), and anole lizard (Anolis carolinensis), for phylogenetic and/or syntenic analyses. Screening of the cDNA library yielded four CYP2 cDNA clones that were phylogenetically classified as CYP2C45, CYP2J25, CYP2AC1, and CYP2AF1. There are numerous newly identified diapsid CYP2 genes that include genes related to the human CYP2Cs, CYP2D6, CYP2G2P, CYP2J2, CYP2R1, CYP2U1, CYP2W1, CYP2AB1P, and CYP2AC1P. Syntenic relationships show that avian CYP2Hs are orthologous to CYP2C62P in humans. CYP2C23 in rats, and Cyp2c44 in mice, and suggest that avian CYP2Hs, along with human CYP2C62P and mouse Cyp2c44, could be renamed as CYP2C23, based upon the nomenclature rules. Analysis of sequence and synteny identifies cormorant and finch CYPs that are apparent orthologs of phenobarbital-inducible chicken CYP2C45. Transcripts of all four cormorant CYP2 genes were detected in the liver of birds from Lake Biwa, Japan. The transcript levels bore no significant relationship to levels of chlorinated organic pollutants in the liver, including polychlorinated biphenyls and dichlorodiphenyltrichloroethane and its metabolites. In contrast, concentrations of perfluorooctane sulfonate and perfluorononanoic acid were negatively correlated with levels of CYP2C45 and/or CYP2J25, suggesting down-regulation of expression by these environmental pollutants. This study expands our view of the phylogeny and evolution of CYP2s, and provides evolutionary insight into the chemical regulation of CYP2 gene expression in diapsids including birds. (C) 2010 Elsevier Inc. All rights reserved.
  • Jin-Seon Lee, Eun-Young Kim, Kohei Iwabuchi, Hisato Iwata
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 153 3 269 - 279 2011年04月 研究論文(学術雑誌) 
    Our previous studies have provided evidence that birds have two isoforms of aryl hydrocarbon receptors (AHR1 and AHR2) and AHR nuclear translocators (ARNT1 and ARNT2) that potentially mediate toxic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. We have also shown that while both in vitro-expressed chicken AHR1 (ckAHR1) and AHR2 (ckAHR2) exhibit binding affinities to TCDD, only ckAHR1 but not ckAHR2 showed a TCDD-dose-dependent transactivation potency of chicken cytochrome P450 1A5 (ckCYP1A5) in in vitro reporter gene assays. To explore the molecular mechanism of functional difference in the two ckAHRs, the present study investigated the molecular characteristics and function of chicken ARNT (ckARNT) that is a potential dimerization partner for the activation of ckAHR. The full-length ckARNT1 and ckARNT2 cDNAs were isolated and their alternative splice variants were also identified. The ckARNT1 transcript was ubiquitously expressed in various tissues, but ckARNT2 showed restricted expressions in brain, kidney and eye, indicating a similar expression pattern to mammalian ARNTs. The expressions of tagged-ckARNT1 and -ckARNT2 were confirmed in a chicken hepatoma LMH cells by western blot analyses, and their interactions with each ckAHR and a specific recognition DNA element, xenobiotic response element (XRE), were examined by gel shift assays. The result showed that ckARNT1 and ckARNT2 dimerize with each ckAHR isoform and bind with the XRE in a TCDD-dependent manner. Hence, we conclude that functional loss on the dimerization with ckARNTs or the XRE binding is not the major cause of the deficient TCDD-dependency of ckAHR2 for the transactivation. Furthermore, in vitro reporter gene assays showed that transfected ckARNT1 failed to modulate the transcriptional induction of ckAHR-mediated ckCYP1A5 gene by TCDD in COS-7 and LMH cells, whereas ckARNT2 could potentiate the TCDD-dependent response in COS-7 but not in LMH cells. This suggests that ckARNT2 has a distinct role from ckARNT1 in AHR signaling pathway and in a cell-specific mode of action. (C) 2010 Elsevier Inc. All rights reserved.
  • Hiroshi Ishibashi, Eun Young Kim, Hisato Iwata
    Environmental Science and Technology 45 7 3123 - 3130 2011年04月 研究論文(学術雑誌) 
    The present study assessed the transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α (BS PPARα) by perfluorochemicals (PFCs) having various carbon chain lengths (C4-C12) using an in vitro reporter gene assay. Among the twelve PFCs treated with a range of 7.8-250 μM concentration, eight perfluoroalkyl carboxylates (PFCAs) and two perfluoroalkyl sulfonates (PFSAs) induced BS PPARα-mediated transcriptional activities in a dose-dependent manner. To compare the BS PPARα transactivation potencies of PFCs, the present study estimated the PFOA induction equivalency factors (IEFs), a ratio of the 50% effective concentration of PFOA to the concentration of each compound that can induce the response corresponding to 50% of the maximal response of PFOA. The order of IEFs for the PFCs was as follows: PFOA (IEF: 1) > PFHpA (0.89) > PFNA (0.61) > PFPeA (0.50) > PFHxS (0.41) > PFHxA (0.38) ≈ PFDA (0.37) > PFBA (0.26) = PFOS (0.26) > PFUnDA (0.15) ≫ PFDoDA and PFBuS (not activated). The structure-activity relationship analysis showed that PFCAs having more than seven perfluorinated carbons had a negative correlation (r = -1.0, p = 0.017) between the number of perfluorinated carbons and the IEF of PFCAs, indicating that the number of perfluorinated carbon of PFCAs is one of the factors determining the transactivation potencies of the BS PPARα. The analysis also indicated that PFCAs were more potent than PFSAs with the same number of perfluorinated carbons. Treatment with a mixture of ten PFCs showed an additive action on the BS PPARα activation. Using IEFs of individual PFCs and hepatic concentrations of PFCs in the liver of wild Baikal seals, the PFOA induction equivalents (IEQs, 5.3-58 ng IEQ/g wet weight) were calculated. The correlation analysis revealed that the hepatic total IEQs showed a significant positive correlation with the hepatic expression levels of cytochrome P450 4A-like protein (r = 0.53, p = 0.036). This suggests that our approach may be useful for assessing the potential PPARα-mediated biological effects of complex mixtures of PFCs in wild Baikal seal population. © 2011 American Chemical Society.
  • Tetsuro Agusa, Junko Fujihara, Haruo Takeshita, Hisato Iwata
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 12 4 2351 - 2382 2011年04月 
    Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways.
  • Jin-Seon Lee, Eun-Young Kim, Koji Nomaru, Hisato Iwata
    TOXICOLOGICAL SCIENCES 119 2 319 - 334 2011年02月 研究論文(学術雑誌) 
    The aryl hydrocarbon receptor (AHR) repressor (AHRR) has been recognized as a negative feedback modulator of AHR-mediated responses in fish and mammals. However, the repressive mechanism by the AHRR has not been investigated in other animals. To understand the molecular mechanism of dioxin toxicity and the evolutionary history of the AHR signaling pathway in avian species, the present study addresses chicken AHRR (ckAHRR). The complementary DNA sequence of ckAHRR encodes an 84-kDa protein sharing 29-52% identities with other AHRRs. High levels of ckAHRR messenger RNA were recorded in the kidney and intestine of nontreated chicks. In hepatoma LMH cells, the 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) 50% effective concentration value for ckAHRR induction (0.0016nM) was the same as that for chicken cytochrome P450 1A5 (ckCYP1A5), implying a shared transcriptional regulation of ckAHRR and ckCYP1A5 by chicken AHR (ckAHR). In ckAHRR transient transfection assays, ckAHRR repressed both ckAHR1- and ckAHR2-mediated transcriptional activities. Deletion and mutation assays revealed that basic helix-loop-helix/Per-ARNT-Sim A domains of ckAHRR, particularly 217-402 amino acid residues, are indispensable for the repression, but the AHR nuclear translocator sequestration by ckAHRR and SUMOylation of ckAHRR are not involved in its repressive mechanism. Additionally, subcellular localization assay of ckAHR1-enhanced green fluorescent protein fusion protein showed that ckAHRR did not affect nuclear translocation of the ckAHR1. Furthermore, ckAHRR inhibited the TCDD- and 17 beta estradiol-enhanced ckCYP1A5 transcription through AHR-estrogen receptor a (ER alpha) cross talk. Taken together, the function of AHRR is conserved in chicken in terms of the negative regulation of AHR and ER alpha activities, but its functional mechanism is likely distinct from those of the mammalian and fish homologues.
  • Eun-Young Kim, Tomoko Suda, Shinsuke Tanabe, Valeriy B. Batoev, Evgeny A. Petrov, Hisato Iwata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 45 4 1652 - 1658 2011年02月 研究論文(学術雑誌) 
    To evaluate the sensitivity and responses to dioxins and related compounds (DRCs) via aryl hydrocarbon receptor (AHR) in Baikal seals (Pusa sibirica), we constructed an in vitro reporter gene assay system. Baikal seal AHR (BS AHR) expression plasmid and a reporter plasmid containing CYP1A1 promoter were transfected in COS-7 cells. The cells were treated with six representative congeners, and dose-dependent responses were obtained for all the congeners. EC(50) values of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 2,3,7,8-TCDF, 2,3,4,7,8-PeCDF, and PCB126 were found to be 0.021, 1.8, 0.16, 2.4, and 2.5 nM, respectively. As the response did not reach the maximal plateau, EC(50) value for PCB118 could not be obtained. The TCDD-EC(50) for BS AHR was as high as that for dioxin sensitive C57BL/6 mouse AHR. The in vitro dose responses were further analyzed following an established systematic framework and multiple (20, 50, and 80%) relative potencies (REPs) to the maximum TCDD response. The estimates revealed lower REP ranges (20-80%) of PeCDD and PeCDF for BS AHR than for mouse AHR. Average of the 20, 50, and 80% REPs was designated as Baikal seal specific TCDD induction equivalency factor (BS IEF). The BS LEFs of PeCDD, TCDF, PeCDF, PCB126, and PCB118 were estimated as 0.010, 0.018, 0.0078, 0.0059, and 0.00010, respectively. Total TCDD induction equivalents (IEQs) that were calculated using BS IEFs and hepatic concentrations in wild Baikal seals corresponded to only 12-31% of 2005 WHO TEF-derived TEQs. Nevertheless, about 50% of Baikal seals accumulated IEQs over the TCDD-EC(50) obtained in this study. This assessment was supported by the enhanced CYP1A1 mRNA expression found in 50% of the specimens contaminated over the TCDD-EC(50). These findings suggest that the IEFs proposed from this in vitro assay could be used to predict AHR-mediated responses in wild seals.
  • Tetsuro Agusa, Kozue Takagi, Todd W. Miller, Reiji Kubota, Yasumi Anan, Hisato Iwata, Shinsuke Tanabe
    ENVIRONMENTAL CHEMISTRY 8 1 19 - 29 2011年 研究論文(学術雑誌) 
    We analysed arsenic (As) compounds in the stomach and intestine contents, bile and urine of green (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) to understand As accumulation through intake and excretion. Stable isotopes of delta N-15 and delta C-13 were also measured for understanding the feeding behaviour dependent accumulation of As. Major As species in gastrointestinal contents were unknown water-soluble As, followed by unextracted As. Concentrations of AB and DMA in the tissues were higher than those in the stomach contents (prey items), indicating high bioaccumulation of these arsenicals. In green turtles, AB concentration was high in bile and increased throughout the gastrointestinal tract, suggesting significant biliary excretion of AB. delta N-15 was positively correlated with AB level in green turtles, whereas a negative relationship between residual As and delta N-15 was observed in hawksbill turtles. This study indicates feeding behaviour-dependent accumulation of As compounds in both turtle species for the first time.
  • Junko Fujihara, Masanori Hasegawa, Rie Kanai, Tetsuro Agusa, Hisato Iwata, Shinsuke Tanabe, Toshihiro Yasuda, Seiji Yamaguchi, Haruo Takeshita
    FORENSIC TOXICOLOGY 29 1 65 - 68 2011年01月 研究論文(学術雑誌) 
    Arsenic trioxide (ATO) is an effective agent for acute promyelocytic leukemia (APL). In this study, the concentrations of dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), As (V), As (III), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and/or serum of a 4-year-old APL patient were followed during ATO treatment. In comparison with a similar analysis previously published for an 85-year-old APL patient, the levels of arsenic compounds and the percentages of MMA and DMA in the present child patient were lower than those of the old patient. Significant positive correlation of 8-OHdG was observed only with DMA, and not with other arsenic compounds. These results are quite different from those of our previous study on an old APL patient during ATO treatment. When arsenic poisoning is diagnosed, it seems important to take into account the differences in the arsenic metabolism according to the ages of subjects. This study is the first to show the relationship between the levels of 8-OHdG and arsenic compounds in urine of a child APL patient treated with ATO.
  • Tetsuro Agusa, Kumiko Nomura, Takashi Kunito, Yasumi Anan, Hisato Iwata, Shinsuke Tanabe
    MARINE POLLUTION BULLETIN 63 5-12 489 - 499 2011年 研究論文(学術雑誌) 
    Nineteen trace elements were determined in liver, muscle, kidney, gonads, and hair of 18 harp seals (Phoca groenlandica) from Pangnirtung in the Baffin Island, Canada. Concentrations of V. Mn, Fe, Cu, Mo, Ag, and Hg in the liver, Co, Cd, and Tl in the kidney, and Ba and Pb in the hair were significantly higher than those in other tissues. Significant positive correlations between Hg concentrations in the hair, and liver, kidney and testis imply usefulness of the hair sample for non-destructive monitoring of Hg in the harp seals. It is suggested that whereas Hg preferentially accumulates in the liver, the accumulation in other tissues is induced at higher hepatic Hg levels. In contrast, Se may not be accumulated in other tissues compared with the liver even at higher hepatic Hg levels because of the presence of excess Se for Hg detoxification in other tissues (C) 2011 Elsevier Ltd. All rights reserved.
  • Kei Nakayama, Itsuki C. Handoh, Shin-Ichi Kitamura, Eun-Young Kim, Hisato Iwata, Shinsuke Tanabe
    SCIENCE OF THE TOTAL ENVIRONMENT 408 23 5824 - 5827 2010年11月 研究論文(学術雑誌) 
    Here we propose a novel microarray data analysis method applicable to evaluation of the chemical effects on wild animals First, we analyzed correlations between log-transformed hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) levels and probe signals detected in wild cormorant liver to screen contaminant-responsive genes Second, principal component analysis (PCA) was conducted using the screened probes Third, these probes were divided into two groups based on our PCA result Finally, we calculated Euclidian distance of signals, which is equivalent to variance of gene expressions, in each probe set, and analyzed the relationship between log-transformed hepatic TEQ levels and Euclidian distances A probe set whereby the calculated Euclidian distance was positively correlated with TEQ levels, could indicate genes that were directly affected by dioxins or other persistent organic pollutants (POPs), hence they can be used as biomarkers By contrast, there were a number of probes whereby the Euclidian distance was negatively correlated with TEQ levels In the latter probe group, the smaller Euclidian distances in highly contaminated individuals could point to changes in physiological activities of wild cormorants Therefore, our microarray data analysis method will provide new insights into POPs-responsive genes in field-collected samples for toxicogenomics studies (C) 2010 Elsevier BV All rights reserved
  • Hisato Iwata, Nobumasa Nagahama, Eun-Young Kim, Michio X. Watanabe, Akiko Sudo
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 152 2 224 - 231 2010年08月 研究論文(学術雑誌) 
    Our previous studies have isolated multiple isoforms of aryl hydrocarbon receptors (AHRs) and AHR nuclear translocators (ARNTs) in avian species. However, roles of such genes on cytochrome P450 1A (CYP1A) expression are not fully understood. To investigate the effects of dioxins on the hepatic expression profiles of AHR1, AHR2, ARNT1 and ARNT2 in avian species, and whether the expression levels of AHRs and ARNTs affect the transcriptions of CYP1A4 and CYP1A5 genes, the eggs of common (great) cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan, were in ovo administrated with 0, 1500 and 4500 pg/g egg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the hepatic expression levels of AHRs, ARNTs and CYP1As in embryos were monitored with two-step real-time RT-PCR. In young and adult cormorants collected from the same location, the hepatic expressions of these genes were also measured to understand the effects of growth stage. The residue levels of TCDD and other chlorinated dioxin-like congeners (DLCs) in the body of cormorants were quantified with high-resolution gas chromatography equipped with mass-spectrometry. There was no observable effect of in ovo TCDD treatment even at the highest dosage on mortality, body weight and morphology of the liver, heart, spleen, kidney and lung in the embryos. The mRNA expression of ARNT2 was slightly suppressed by the treatment with TCDD, while no alteration was observed for the expression of AHR1. AHR2 and ARNT1. Expressions of CYP1A4 and CYP1A5 were dose-dependently enhanced by TCDD, but CYP1A4 mRNA level increased more prominently than CYP1A5, indicating the difference in induction efficiency between the CYP1A isozymes. Comparison of hepatic mRNA levels of these genes among embryonic, young and adult cormorants revealed that young and adult cormorants had greater CYP1A5 expression levels than embryos, independently of the accumulation levels of DLCs. These results suggest that the hepatic induction of each CYP1A by DLCs in cormorants occurs in an isoform-specific manner and CYP1A5 expression, at least partially, depends on the factors related to the growth of cormorants, but the transcriptional processes of CYP1A5 are not related to the expression levels of AHRs and ARNTs. This study yielded results supporting our previous observations that in reality, high accumulation of DLCs induces hepatic CYP1A4 and 1A5 expressions in the wild cormorant population. (C) 2010 Elsevier Inc. All rights reserved.
  • Michio X. Watanabe, Tatsuya Kunisue, Lin Tao, Kurunthachalam Kannan, Annamalai Subramanian, Shinsuke Tanabe, Hisato Iwata
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 29 7 1551 - 1560 2010年07月 研究論文(学術雑誌) 
    Dioxins and related compounds (DRCs) and perfluorinated compounds were measured in the livers of pigs (Sus scrofa) collected from an open waste dumping site in South India. Hepatic concentrations of DRCs and perfluorooctanesulfonate (PFOS; up to 200 ng/g wet wt) were significantly higher in male and female pigs, respectively, collected from the dumping site than in those from a reference site. Results suggest that dumping sites are a source of DRCs and PFOS. Hepatic concentrations of DRCs in piglets were higher than in mothers, especially for the congeners with molecular weights in the range of 360 to 400, implying congener-specific maternal transfer of DRCs in swine. Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans and some non-ortho dioxin-like polychlorinated biphenyls (PCBs) in the liver of pigs were higher than those in the adipose fat and muscle of the same specimens. In addition, the liver-to-adipose concentration ratios for each congener had a significant positive correlation with the levels of hepatic cytochrome P450 (CYP)1A-like protein, suggesting congener-specific and CYP1A-dependent hepatic sequestration of DRCs in the swine. Total hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs; 8.9-350 pg/g fat wt) had a significant positive correlation with CYP1A-like protein expression (r= 0.56, p = 0.012), suggesting the induction of CYP1A by DRCs. However, the total TEQs had a significant negative correlation with CYP4A-like protein (r= -0.49, p= 0.029), suggesting repression of peroxisome proliferator-activated receptor-alpha (PPAR alpha)-mediated signaling pathway by DRCs. Decreases in plasma total thyroxine (T(4)), free T(4), and immunoglobulin (Ig) G were also found in pigs from the dumping site compared with those from the reference site. This study provides insight into the toxicological impacts of DRCs and perfluorinated compounds in wild animals from open waste dumping sites. Environ. Toxicol. Chem. 2010;29:1551-1560. (C) 2010 SETAC
  • Akira Kubota, Mafumi Watanabe, Tatsuya Kunisue, Eun-Young Kim, Shinsuke Tanabe, Hisato Iwata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 44 9 3559 - 3565 2010年05月 研究論文(学術雑誌) 
    The present study assesses effects of dioxins and related compounds (DRCs) including polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls (DL-PCBs) on cytochrome P450 1A (CYP1A) expression level in liver of black-footed albatrosses (Phoebastria nigripes) collected from the North Pacific, Total 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-T4CDD) toxic equivalents (TEQs) derived from toxic equivalency factor for birds proposed by World Health Organization were in the range of 2100 to 10 000 pg/g lipid wt (120-570 pg/g wet wt). Simultaneously, microsomal alkoxyresorufin O-dealkylase (AROD) activities, including methoxy-, ethoxy-, pentoxy-, and benzyloxy-resorufin O-dealkylase activities were also measured in the same specimens. Total TEQs and TEQ (on wet wt basis) from some individual DRC congeners had significant positive correlations with AROD activities, suggesting induction of CYP1A by DRCs. Congeners like 2,3,7,8-T4CDD and most of the DL-PCBs that showed no significant positive correlations between the concentrations and AROD activities, exhibited significant negative correlations between AROD activities and the concentration ratio of the congener to a recalcitrant CB169, suggesting preferential metabolism of these congeners by induced CYP1A. As far as we know, this is the first direct evidence revealing that hepatic CYP1A level is elevated with the accumulation of DRCs in the wild black-footed albatross population. The present study gives more robust estimate of impacts of DRCs on CYP1A induction in this rare pelagic species than indexes like hazard quotient and TEQ-threshold comparison that have been so far carried out.
  • Tetsuro Agusa, Hisato Iwata, Junko Fujihara, Takashi Kunito, Haruo Takeshita, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, Shinsuke Tanabe
    TOXICOLOGY AND APPLIED PHARMACOLOGY 242 3 352 - 362 2010年02月 研究論文(学術雑誌) 
    To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for CST omega 1 (GSTO1) A1a140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega 2 (GSTO2) Asn142Asp, CST pi 1 (GSTP1) Ile105Val, GST mu 1 (GSTM1) wild/null, and GST theta 1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu 155del hetero type showed higher urinary concentration of As(V) than the wild homo type. Higher percentage of DMA(V) in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As(V) to As(III). Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of CST superfamily with arsenic metabolism in a Vietnamese population. (C) 2009 Elsevier Inc. All rights reserved.
  • Interindividual variation in arsenic metabolism in a Vietnamese population: association with 17 single nucleotide polymorphisms in AS3MT.
    Agusa, T, Iwata, H, Fujihara, J, Kunito, T, Takeshita, H, Minh, T.B, Trang, P.T.K, Viet, P.H, Tanabe, S
    In: Hamamura, N., Suzuki, S., Mendo, S., Barroso, C.M., Iwata, H., Tanabe, S. (Eds.), Biological Responses to Chemical Contaminants: From Molecular to Community Level (Interdisciplinary Studies on Environmental Chemistry Vol. 3), Global COE Program, Eh… 113-119  2010年 
    In: Hamamura, N., Suzuki, S., Mendo, S., Barroso, C.M., Iwata, H., Tanabe, S. (Eds.), Biological Responses to Chemical Contaminants: From Molecular to Community Level (Interdisciplinary Studies on Environmental Chemistry Vol. 3), Global COE Program, Ehime University, TERRAPUB, Tokyo
  • Tetsuro Agusa, Takashi Kunito, Reiji Kubota, Suguru Inoue, Junko Fujihara, Tu Binh Minh, Nguyen Ngoc Ha, Nguyen Phuc Cam Tu, Pham Thi Kim Trang, Chhoun Chamnan, Haruo Takeshita, Hisato Iwata, Bui Cach Tuyen, Pham Hung Viet, Touch Seang Tana, Shinsuke Tanabe
    Reviews on Environmental Health 25 3 193 - 220 2010年 
    In this review, we summarize the current knowledge on exposure, metabolism, and health effects of arsenic (As) in residents from As-contaminated groundwater areas of Vietnam and Cambodia based on our findings from 2000 and other studies. The health effects of As in humans include severe gastrointestinal disorders, hepatic and renal failure, cardiovascular disturbances, skin pigmentation, hyperkeratosis, and cancers in the lung, bladder, liver, kidney, and skin. Arsenic contamination in groundwater is widely present at Vietnam and Cambodia and the highest As levels are frequently found in groundwater from Cambodia. Sand filter system can reduce As concentration in raw groundwater. The results of hair and urine analyses indicate that residents from these As-contaminated areas are exposed to As. In general, sex, age, body mass index, and As exposure level are significantly associated with As metabolism. Genetic polymorphisms in arsenic (+III) methyltransferase and glutathione-5-transferase isoforms may be influenced As metabolism and accumulation in a Vietnamese population. It is suggested oxidative DNA damage is caused by exposure to As in groundwater from residents in Cambodia. An epidemiologic study on an association of As exposure with human health effects is required in these areas. © 2010 Freund Publishing House Limited.
  • Hiroki Sakai, Eun-Young Kim, Evgeny A. Petrov, Shinsuke Tanabe, Hisato Iwata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 43 16 6391 - 6397 2009年08月 研究論文(学術雑誌) 
    To characterize ligand-dependent transcriptional activation of constitutive active/androstane receptor (CAR) in aquatic mammals, transactivation potentials of the Baikal seal (Pusa sibirica) CAR (bsCAR) by environmental pollutants, including persistent organic pollutants (POPs) and brominated flame retardants (BFRs), were investigated using an in vitro reporter gene assay, and compared with those of the mouse CAR (mCAR). Measurement of luciferase reporter gene activities demonstrated that the seal CAR was activated by POPs, including a technical mixture of PCBs (Kanechlor-500), certain individual PCB congeners, DOT compounds, and trans-nonachlor. No or slight bsCAR-dependent activity was detected in experiments with PBDE congeners and HBCDs. The interspecies comparison of lowest observed effect concentration (LOEC) for CAR transactivation by each compound revealed that bsCAR responds more sensitively to PCBs than mCAR. In addition, bsCAR was weakly deactivated by PBDE99, whereas mCAR transcriptional activity decreased weakly by PBDE100, PBDE154, and PBDE187. Comparison of reporter gene activities by the congeners with the same IUPAC numbers among PCBs and PBDEs revealed that both bsCAR and mCAR were not activated by PBDE99 and PBDE153, but were activated by PCB99 and PCB153. The small ligand-binding pocket in CAR may contribute to difference in response between PCBs and PBDEs. Given that ethical rationale prevents dosing studies with such organohalogens in aquatic Mammals, Our in vitro assay system constructed with CAR cDNA from a species of interest provides a useful and realistic alternative approach in ecotoxicology.
  • Michio X. Watanabe, Stephanie P. Jones, Hisato Wata, Eun-Young Kim, Sean W. Kennedy
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 149 4 605 - 612 2009年05月 研究論文(学術雑誌) 
    In this study we investigated the effect of a single-compound exposure or two compound co-exposure to tetrachlorodibenzo-p-dioxin (TCDD) plus perfluorooctane sulfonate (PFOS) OF perfluorooctanoic acid (PFOA) on the mRNA expression of cytochromes P450 (CYP) 1A4, 4V2 and 3A37, ethoxyresorufin-O-deethylase (EROD) activity and cell viability in chicken (Gallus gallus domesticus) embryo primary hepatocyte cultures. Cell viability after 24 h Of incubation was significantly decreased in cells exposed to PFOS at concentrations between 30 mu M and 60 mu M with or without co-exposure to TCDD (0.3 nM at maximum). PFOA did not decrease cell viability even at maximum concentrations of 60 mu M. TCDD induced CYP1A4 mRNA and EROD activity substantially as reported previously. PFOS also increased CYP1A4 mRNA in a concentration-dependent manner. Co-exposure of cells to PFOS plus TCDD did not change CYP1A4 mRNA levels compared to cells treated with TCDD alone. PFOS alone did not induce CYP4V2 mRNA, however 40-50 mu M PFOS Plus TCDD (0.3 nM) induced CYP4V2 mRNA compared to TCDD alone (P < 0.05). This trend was similar to that observed with cc-exposure to TCDD Plus PFOA, suggesting that PFOA alone did not induce CYP4V2 mRNA. whereas co-exposure to TCDD plus PFOA induced the expression levels. PFOS alone decreased CYP3A37 mRNA by a maximum of 45%. however after co-exposure to TCDD, recovery of mRNA expression to levels measured in DMSO-treated cells was observed. Our data Suggest a complex gene response to mixtures of dioxin-like and perfluorinated compounds. (c) 2009 Elsevier Inc. All rights reserved.
  • Akira Kubota, Eun-Young Kim, Hisato Iwata
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 149 4 544 - 551 2009年05月 研究論文(学術雑誌) 
    Here we report the inter-paralog comparison of cytochrome P4501A (CYP1A) catalytic function in common cormorant (Phalacrocorax carbo) using the recombinant proteins synthesized by yeast-based vector system. CYP1A4 and CYP1A5 proteins from common cormorant were heterologously expressed in yeast Saccaromyces cerevisiae. Kinetic analyses revealed that among alkoxyresorufin (methoxy-, ethoxy-, pentoxy- and benzyloxyresorufin) O-dealkylase (AROD) activities V(max) value for ethoxyresorufin O-deethylase (EROD) activity was the highest for both enzymes. reaching 0.91 +/- 0.034 and 1.8 +/- 0.043 nmol/min/nmol CYP for CYP1A4 and CYP1A5, respectively. Similar results were obtained for the catalytic efficiencies represented as the ratios of V(max) to K(m) (V(max)/K(m)). Meanwhile, distinct substrate preferences were also observed; CYP1A4 had V(max) and V(max)/K(m) values for benzyloxyresorufin O-debenzylase (BROD) activity 12- and 46-fold greater than CYP1A5, respectively, while CYP1A5 was about 13- and 4.5-fold more efficient in methoxyresorufin O-demethylase (MROD) activity than CYP1A4. The K(m) values showed no significant change among MROD, EROD, pentoxyresorufin O-depenthylase (PROD) and BROD activities for both enzymes, except for significant differences between PROD and other three activities for CYP1A4. Comparing the results in the present study with previous studies addressing chicken and rat CYP1A enzymes, it is also clear that CYP1A orthologs have different catalytic preferences for AROD activities between cormorant and rat and even between cormorant and chicken. Variations in CYP1A catalytic function between cormorant CYP1A paralogs and between CYP1A orthologs from cormorant and other species indicate that enzymatic properties should be characterized on the basis not only of a limited model species such as chicken, but also of multiple species to further understand the mechanism underlying differences in substrate selectivity and the interaction with environmental contaminants in avian species. (c) 2008 Elsevier Inc. All rights reserved.
  • Tetsuro Agusa, Hisato Iwata, Junko Fujihara, Takashi Kunito, Haruo Takeshita, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, Shinsuke Tanabe
    TOXICOLOGY AND APPLIED PHARMACOLOGY 236 2 131 - 141 2009年04月 研究論文(学術雑誌) 
    To elucidate the role of genetic factors in arsenic (As) metabolism, we studied associations of single nucleotide polymorph isms (SNPs) in As (+3 oxidation state) methyltransferase (AS3MT) with the As concentrations in hair and urine, and urinary As profile in residents in the Red River Delta, Vietnam. Concentrations of total As in groundwater were 0.7-502 mu g/l. Total As levels in groundwater drastically decreased by using sand filter, indicating that the filter could be effective to remove As from raw groundwater. Concentrations of inorganic As (IAs) in urine and total As in hair of males were higher than those of females. A significant positive correlation between monomethylarsonic acid (MMA)/IAs and age in females indicates that older females have higher methylation capacity from IAs to MMA. Body mass index negatively correlated with urinary As concentrations in males. Homozygote for SNPs 4602AA, 35991GG, and 37853GG, which showed strong linkage disequilibrium (LD), had higher percentage (%) of dimethylarsinic acid (DMA) in urine. SNPs; 4740 and 12590 had strong LD and associated with urinary %DMA. Although SNPs 6144, 12390, 14215, and 35587 comprised LD cluster, homozygotes in SNPs 12390GG and 35587CC had lower DMA/MMA in urine, suggesting low methylation capacity from MMA to DMA in homo types for these SNPs. SNPs 5913 and 8973 correlated with %MMA and %DMA, respectively. Heterozygote for SNP 14458TC had higher MMA/IAs in urine than TT homozygote, indicating that the heterozygote may have stronger methylation ability of IAs. To our knowledge, this is the first study on the association of genetic factors with As metabolism in Vietnamese. (C) 2009 Elsevier Inc. All rights reserved.
  • Daisuke Imaeda, Tatsuya Kunisue, Yoko Ochi, Hisato Iwata, Oyuna Tsydenova, Shin Takahashi, Masao Amano, Evgeny A. Petrov, Valeriy B. Batoev, Shinsuke Tanabe
    ENVIRONMENTAL POLLUTION 157 3 737 - 747 2009年03月 研究論文(学術雑誌) 
    This study investigated the accumulation features and temporal trends of PCDD/Fs, dioxin-like PCBs (DL-PCBs) and non-dioxin-like PCBs (NDL-PCBs) in the blubber of Baikal seals collected in 1992 and 2005. DL-PCBs (480-3600 ng/g) and NDL-PCBs (980-35,000 ng/g) were dominant contaminants. Concentrations of PCDDs and PCBs in males were significantly higher than in females. In males, age-dependent accumulation was observed for PCDDs, mono-ortho PCBs and NDL-PCBs. PCDFs and non-ortho PCBs showed no such trends, implying that exposure of seals to these contaminants has been decreasing in recent years. No decreasing temporal trend was observed for PCDDs, mono-ortho PCBs and NDL-PCBs, suggesting that Baikal seals are still exposed to PCDDs and PCBs. TEQs of PCDDs and mono-ortho PCBs in seals collected in 2005 accounted for 62-77% of total TEQs. The TEQ levels in 40% of the specimens exceeded the threshold level for immunosuppression observed in harbor seals (209 pg/g). (C) 2008 Elsevier Ltd. All rights reserved.
  • Tetsuro Agusa, Suguru Inoue, Takashi Kunito, Tu Binh Minh, Nguyen Ngoc Ha, Nguyen Phuc Cam Tu, Pham Thi Kim Trang, Hisato Iwata, Pham Hung Viet, Bui Cach Tuyen, Shinsuke Tanabe
    International Journal of Environmental Studies 66 1 49 - 57 2009年02月 研究論文(学術雑誌) 
    Groundwater contamination by arsenic is a serious environmental problem in the world. Yet there have been few studies conducted in Southeast Asian countries. This article surveys arsenic contamination in groundwater and residents from Vietnam, and is based on our previous studies. Samples of groundwater (n = 118), human hair (n = 59), and urine (n = 100) were collected in the Red River and Mekong River Deltas during 2001-2004. Arsenic was detected in most of the groundwater samples, and its level ranged from < 0.1 to 486 μg/l. Elevated concentrations of arsenic were observed in groundwater at some locations in Ha Nam (up to 486 μg/l) in the Red River Delta and Dong Thap (up to 411 μg/l) in the Mekong River Delta. Remarkably, about 33% of these groundwater samples exceeded the WHO drinking water guideline of 10 μg/l. These results suggest that arsenic contamination in groundwater may be widely present in both the Red River and Mekong River Deltas, Vietnam. A significant positive correlation was observed between arsenic concentrations in groundwater and human hair. Arsenic speciation of human urine revealed the presence of inorganic arsenic, and these concentrations positively correlated with arsenic levels in groundwater. Thus, it is likely that residents in our study areas are chronically exposed to arsenic through drinking groundwater, suggesting that there is a health risk from arsenic in Vietnam.
  • FUJIHARA Junko, AGUSA Tetsuro, TANAKA Junko, FUJII Yoshimi, MORITANI Tamami, HASEGAWA Masanori, IWATA Hisato, TANABE Shinsuke, TAKESHITA Haruo
    Forensic Toxicology 27 1 41 - 44 2009年02月 研究論文(学術雑誌) 
    8-hydroxy-2’ –deoxyguanosine (8-OHdG) as a possible marker of arsenic posoning: A clinical case study on the relationship between concentrations of 8-OHdG and each arsenic compound in urine of an acute promyelocytic leukemia patient being treated with arsenic trioxide
  • Tetsuro Agusa, Takashi Kunito, Tu Binh Minh, Pham Thi Kim Trang, Hisato Iwata, Pham Hung Viet, Shinsuke Tanabe
    ENVIRONMENTAL POLLUTION 157 2 396 - 403 2009年02月 研究論文(学術雑誌) 
    This study investigated the status of arsenic (As) exposure from groundwater and rice, and its methylation capacity in residents from the Red River Delta, Vietnam. Arsenic levels in groundwater ranged from <1.8 to 486 mu g/L Remarkably, 86% of groundwater samples exceeded WHO drinking water guideline of 10 mu g/L Also, estimated inorganic As intake from groundwater and rice were over Provisional Tolerable Weekly Intake (15 mu g/week/kg body wt.) by FAO/WHO for 92% of the residents examined. Inorganic As and its metabolite (monomethylarsonic acid and dimethylarsinic acid) concentrations in human urine were positively correlated with estimated inorganic As intake. These results suggest that residents in these areas are exposed to As through consumption of groundwater and rice, and potential health risk of As is of great concern for these people. Urinary concentration ratios of dimethylarsinic acid to monomethylarsonic acid in children were higher than those in adults, especially among men, indicating greater As methylation capacity in children. (C) 2008 Elsevier Ltd. All rights reserved.
  • Jin-Seon Lee, Eun-Young Kim, Hisato Iwata
    TOXICOLOGY AND APPLIED PHARMACOLOGY 234 1 1 - 13 2009年01月 研究論文(学術雑誌) 
    The present study focuses on the molecular mechanism and interspecies differences in susceptibility of avian aryl hydrocarbon receptor (AHR)-cytochrome P4501A (CYP1A) signaling pathway. By the cloning of 5′-flanking regions of CYP1A5 gene from common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus), seven putative xenobiotic response elements (XREs) were identified within 2.7 kb upstream region of common cormorant CYP1A5 (ccCYP1A5), and six XREs were found within 0.9 kb of chicken CYP1A5 (ckCYP1A5). Analysis of sequential deletion and mutagenesis of the binding sites in avian CYP1A5 genes by in vitro reporter gene assays revealed that two XREs at -613 bp and -1585 bp in ccCYP1A5, and one XRE at -262 bp in ckCYP1A5 conferred TCDD-responsiveness. The binding of AHR1 with AHR nuclear translocator 1 (ARNT1) to the functional XRE in a TCDD-dependent manner was verified with gel shift assays, suggesting that avian CYP1A5 is induced by TCDD through AHR1/ARNT1 signaling pathway as well as mammalian CYP1A1 but through a distinct pathway from mammalian CYP1A2, an ortholog of the CYP1A5. TCDD-EC50 for the transcriptional activity in both cormorant AHR1- and AHR2-ccCYP1A5 reporter construct was 10-fold higher than that in chicken AHR1-ckCYP1A5 reporter construct. In contrast, chicken AHR2 showed no TCDD-dependent response. The TCDD-EC50 for CYP1A5 transactivation was altered by switching AHR1 between the two avian species, irrespective of the species from which the regulatory region of CYP1A5 gene originates. Therefore, the structural difference in AHR, not the CYP1A5 regulatory region may be a major factor to account for the dioxin susceptibility in avian species. © 2008 Elsevier Inc. All rights reserved.
  • Dong-Ha Nam, Eun-Young Kim, Hisato Iwata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 42 24 9391 - 9396 2008年12月 研究論文(学術雑誌) 
    To assess the inducibility of avian metallothionein (MT) genes and potential tolerability of their protiens to element exposure, we investigated the transcriptional inducibilities of cormorant (Phalacrocorax carbo) and mallard (Anas platyrhynchos) MT genes in CV-1 cells by elements and detoxification potencies of their in vitro synthesized MT proteins. About 1.3 kb of 5'-upstream regions were sequenced for cormorant MT1 and 2 genes, where two metal-responsive elements were identified. Both cormorant MT promoters were dose dependently activated by Cd, Zn, Cu, and CH(3)Hg, whereas no transactivation was detected by Pb, Tl, Ag, inorganic Hg, Cr(VI), Cr(III), As(V), As(III), Ni, Co, Rb, and Bi, suggesting a shared transactivational mechanism of both MTs for specific elements. These findings support our previous results, where Cu and Zn concentrations were shown to be positively correlated with hepatic MT1/2 mRNA levels in wild cormorants. Comparison of EC(50) and LOEL (lowest observed effect level) for each element revealed that Cd was the most potent inducer of MT1/2 promoters, followed by CH3Hg, Zn, and Cu. Since LOELs of CH(3)Hg for both MT promoters were higher than the hepatic levels in wild cormorants, hepatic CH3Hg concentration may not be high enough to induce MT mRNA in the wild population. Although LOELs of Cd were much lower than the hepatic concentrations detected in wild cormorants, no significant correlation was observed between hepatic Cd levels and MT mRNAs. This may be due to the masking effect of multiple elements, probably by Zn and/or Cu that were highly accumulated in wild cormorants. Cotreatment of Cd with Zn supported a possible suppression of Cd-induced MT expression by Zn in wild cormorants. MT1 and 2 proteins of cormorant and mallard endowed Escherichia coli with significantly higher growth rate than control to Cd exposure (500-1000 mu M), implying that avian MTs could be involved in the detoxification of intracellular Cd. This study provides the first evidence on the inducibility of avian MT isoforms by specific elements and functional significance of each avian MT isoform in detoxifying intracellular heavy metals. Our in vitro approaches demonstrate their validity in predicting the response of MTs to element exposure in a wild avian population.
  • Kei Nakayama, Hisato Iwata, Lin Tao, Kurunthachalam Kannan, Mai Imoto, Eun-Young Kim, Kosuke Tashiro, Shinsuke Tanabe
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 27 11 2378 - 2386 2008年11月 研究論文(学術雑誌) 
    Contamination levels of perfluorinated compounds (PFCs), including perfluorooctanesulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorooctane sulfonamide (PFOSA), perfluorohexanesulfonate (PFHS), and perfluorooctanoic acid (PFOA), were determined in the livers of wild common cormorants (Phalacrocorax carbo) from Lake Biwa, Japan. Potential effects of PFCs alone and combined effects by complex mixture of PFCs and dioxins and related compounds (DRCs) were also assessed by gene expression profiling using a cormorant oligo array. Perfluorooctanesulfonate, PFNA, and PFOSA were detected in almost all liver samples analyzed, while concentrations of PFHS and PFOA were below the limit of quantification. The microarray data analyses revealed that hepatic PFC levels were correlated with the expression of 74 genes. Real-time reverse-transcript polymerase chain reaction data demonstrated that PFOS concentration was positively correlated with mRNA levels of glutathione peroxidase 1 and glutathione S-transferase alpha 3 and negatively correlated with levels of heat shock 70-kDa protein 8 and tumor rejection antigen 1 mRNAs. These results suggest the induction of antioxidant enzymes in response to oxidative stress caused by PFCs and the suppression of molecular chaperones, leading to reduction in protein stability. Moreover, multiple regression analyses identified seven significant models in which certain genes showed expression levels altered by accumulation of PFCs and DRCs. The regression models explained associations with cytochrome P450 1A mRNA and protein expression levels, and its catalytic activity, ethoxyresorufin-O-deethylase of both PFNA and the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent levels. Thus, the regression models suggested the potential of PFCs to enhance toxicities of DRCs. Since mixture toxicity is an urgent issue, further study is required to understand the effects of mixtures of PFCs and DRCs in wild cormorants.
  • Akira Kubota, Hisato Iwata, Eun-Young Kim
    MARINE ENVIRONMENTAL RESEARCH 66 1 154 - 155 2008年07月 研究論文(学術雑誌) 
    The present study clarifies the enzymatic properties of two avian cytochrome P4501A (CYP1A) paralogs, CYPIA4 and 1A5, using a yeast-based vector system. Recombinant CYP1A4 and 1A5 Proteins from common cormorant (Phalacrocorax carbo) were expressed in yeast cells, and showed typical reduced CO-difference spectra with a peak at 446 nm. Kinetic analysis of O-dealkylase of methoxy-, ethoxy-, pentoxy-and benzyloxyresorufin catalyzed by the CYP1A enzymes revealed that V-value for ethoxyresorufin-O-deethylase (EROD) activity was much higher than that for the other three O-dealkylase activities for both isozymes. Interestingly, remarkable substrate specificity of the CYP1As was observed for O-clealkylation of benzyloxyresorufin and methoxyresorufin; CYP1A4 was highly specific for catalyzing benzyloxyresorufin-O-debenzylase activity, whereas CYP1A5 was more efficient in catalyzing methoxyresorufin-O-demethylase activity. The present study also measured CYP1A-dependent EROD activity in the presence of 2,3,7,8-tetrachlorodibenzofuran (TCDF) to evaluate the ability of this dioxinlike congener to inhibit the EROD activity. One hundred nanomolar TCDF noncompetitively inhibited CYP1A5-dependent EROD activity, although no inhibitory effect was detected for CYPlA4-dependent EROD activity. These results indicate that the avian CYP1A paralogs have different affinities for substrate and inhibitor, thus suggesting their distinct physiological and toxicological roles. (C). 2008 Elsevier Ltd. All rights reserved.
  • Tetsuro Agusa, Kozue Takagi, Reiji Kubota, Yasumi Anan, Hisato Iwata, Shinsuke Tanabe
    ENVIRONMENTAL POLLUTION 153 1 127 - 136 2008年05月 研究論文(学術雑誌) 
    Concentrations of total arsenic (As) and individual compounds were determined in green and hawksbill turtles from Ishigaki Island, Japan. In both species, total As concentrations were highest in muscle among the tissues. Arsenobetaine was a major compound in most tissues of both turtles. High concentrations of trimethylarsine oxide were (]elected in hawksbill turtles. A significant negative correlation between standard carapace length (SCL), an indicator of age, and total As levels in green turtles was found. In contrast, the levels increased with SCL of hawksbill turtles. Shifts in feeding habitats with growth may account for such a growth-dependent accumulation of As. Although concentrations of As in marine sponges, the major food of hawksbill turtles are not high compared to those in algae eaten by green turtles, As concentrations in hawksbill turtles were higher than those in green turtles, indicating that hawksbill turtles may have a specific accumulation mechanism for As. (C) 2007 Elsevier Ltd. All rights reserved.
  • ISHIBASHI Hiroshi, IWATA Hisato, KIM Eun-Young, TAO Lin, KANNAN Kurunthachalam, TANABE Shinsuke, BATOEV Valeriy B, PETROV Evgeny A
    Environmental Science and Technology 42 7 2302 - 2308 2008年04月 研究論文(学術雑誌) 
    To investigate the biological effects of perfluorochemicals (PFCs) and to identify biomarkers of exposure to PFCs, this study focused on the effects mediated by peroxisome proliferator-activated receptor α (PPARα) in Baikal seals (Pusa sibirica). We cloned a full-length cDNA, encoding PPARα from the liver of Baikal seal, which has a deduced open reading frame of 468-amino acid residues with a predicted molecular mass of 52.2 kDa. Comparison of the amino-acid sequence of Baikal seal PPARα with that of other mammalian PPARα showed considerable similarities with PPARα of dog (97%), human (95%), rat (92%), and mouse (91%). The quantitative real-time RT-PCR analyses of tissues from Baikal seals revealed that PPARα mRNAs were primarily expressed in the liver, kidney, heart, and muscle. The hepatic expression levels of PPARα mRNA showed a positive correlation with the expression levels of immunochemically detected cytochrome P450 (CYP) 4A-like protein, indicating that the PPARα-CYP4A signaling pathway in Baikal seal is likely conserved. This study also developed an in vitro PPARα reporter gene assay using African green monkey kidney CV-1 cells transiently transfected with Baikal seal PPARα cDNA expression vector and a reporter vector containing a peroxisome proliferator-responsive element. The in vitro reporter gene assay displayed significant response to clofibrate, which is a known PPARα agonist in humans and rodents. Treatment with perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), or perfluorooctane sulfonate (PFOS) induced PPARα-mediated transcriptional activity in a dose-dependent manner, showing the lowest-observed-effect concentrations of 62.5, 125, 125, 62.5, and 125 μM, respectively. In the livers of wild Baikal seals, expression levels of PPARα mRNA showed a significant positive correlation with PFNA levels. Moreover, expression of hepatic CYP4A-like protein was significantly correlated with the hepatic concentrations of PFNA and PFDA. These results suggest modulation of the PPARα-CYP4A signaling pathway by PFCs in the wild Baikal seals. Our study demonstrates that the PPARα-mediated response may be a useful biomarker to evaluate potential biological effects of PFCs in wildlife. © 2008 American Chemical Society.
  • Hiroshi Ishibashi, Hisato Iwata, Eun-Young Kim, Lin Tao, Kurunthachalam Kannan, Masao Amano, Nobuyuki Miyazaki, Shinsuke Tanabe, Valeriy B. Batoev, Evgeny A. Petrov
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 42 7 2295 - 2301 2008年04月 研究論文(学術雑誌) 
    Concentrations of perfluorochemicals (PFCs) including perfluoroalkylsulfonates (PFSAs) and perfluoroalkylcarboxylates (PFCAs) were determined in liver and serum of Baikal seals (Pusa sibirica) collected from Lake Baikal, Russia in 2005. Among the 10 PFC compounds measured, perfluorononanoic acid (PFNA, 3.3-72 ng/g wet wt) concentrations were the highest in liver, followed by perfluorooctanesulfonate (PFOS, 2.6-38 ng/g). The accumulation profile of long-chain (C7-C12) PFCAs in particular, the predominance of PFNA, indicated that 8:2 fluorotelomer alcohol or commercially manufactured PFNA is a major local source of PFCs in Lake Baikal. No gender-related differences in the concentrations of individual PFCs or total PFCs were found. Tissues from pups and juveniles contained relatively higher concentrations of PFCs than tissues from subadults and adults, suggesting that maternal transfer of PFCs is of critical importance, Comparison of concentrations of PFCs in livers and sera collected from the same individuals of Baikal seals revealed that residue levels of PFOS, PFNA, perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were significantly higher in liver than in serum. The concentration ratios of PFNA and PFDA between liver and serum were calculated to be 14 and 15, respectively, whereas the ratio of PFOS was 2.4. This suggests preferential retention of both PFNA and PFDA in liver. Concentrations of PFOS, PFNA, and PFDA in liver were significantly correlated with those in serum, whereas concentrations of PFUnDA were not correlated in between the two tissues, suggesting differences in pharmacokinetics among these PFCs. Temporal comparisons of hepatic PFC concentrations in seals collected between 1992 and 2005 showed that the concentrations of PFOS (p = 0.0006), PFNA (p = 0.061) and PFDA (p = 0.017) were higher in animals collected in recent years, indicating ongoing sources of PFC contamination in Lake Baikal.
  • Hydroxylated polychlorinated biphenyls in the blood of Baikal seals (Pusa Sibirica)
    Imaeda, D, Kunisue, T, Iwata, H, Tsydenova, O, Takahashi, S, Nomiyama, K, Amano, M, Petrov, A.E, Batoev, B.V, Tanabe, S
    Organohalogen Compounds 70 1475 - 1478 2008年 [査読有り]
     
    Proceedings
  • 宇高真行, 池本徳孝, 岩田久人, 高橋 真, Batoev, V. B, Petrov, E. A, 田辺信介
    環境毒性学会誌 11 2 117 - 131 2008年 [査読有り]
  • Tetsuro Agusa, Junko Fujihara, Haruo Takeshita, Hisato Iwata, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, Shinsuke Tanabe
    Biomedical Research on Trace Elements 19 3 265 - 267 2008年
  • Tetsuro Agusa, Kozue Takagi, Hisato Iwata, Shinsuke Tanabe
    Biomedical Research on Trace Elements 19 1 63 - 66 2008年
  • 仲山 慶, 酒井 大樹, 北村 真一, 須藤 明子, 金 恩英, 田辺 信介, 岩田 久人
    環境毒性学会誌 11 2 75 - 81 2008年
  • Tetsuro Agusa, Kumiko Nomura, Takashi Kunito, Yasumi Anan, Hisato Iwata, Nobuyuki Miyazaki, Ryo Tatsukawa, Shinsuke Tanabe
    MARINE POLLUTION BULLETIN 57 6-12 807 - 815 2008年 研究論文(学術雑誌) 
    Concentrations of 19 trace elements (V, Cr, Mn, Fe, Co, Cu, Zn, Se, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, Tl, Hg, and Pb) were determined in the liver of the striped dolphins (Stenella coeruleoalba) collected around Japan during 1977-1982 to examine the sex difference, age dependence, and interrelationships among trace elements. Tissue distribution of trace elements was also investigated in one adult and one fetus specimens. Generally, concentrations of Se, Sr, Ag, Cd, Cs, Ba, Hg, and Pb were higher in the tissues of adult than those of fetus, whereas the opposite trend was observed for Cr and Tl. There were no significant sex differences in the trace element levels in the liver. Significant positive correlations between age (0-26.5 years) and hepatic concentrations were found for Ag, Se, Hg, V, Fe, Pb, and Sr, suggesting their age-dependent accumulation in the liver. In contrast, hepatic concentrations of Mn and Zn decreased with age. Significant positive relationships were observed between Se, and Hg, Ag, V, Fe, and Sr in the liver. (C) 2008 Elsevier Ltd. All rights reserved.
  • Tetsuro Agusa, Kozue Takagi, Hisato Iwata, Shinsuke Tanabe
    MARINE POLLUTION BULLETIN 57 6-12 782 - 789 2008年 研究論文(学術雑誌) 
    Total arsenic (As) and its compounds were determined in liver, kidney, muscle, and stomach contents of green turtles (Chelonia mydas). Total As concentrations in the muscle were higher than those in the kidney and liver. Arsenobetaine (AB) was the predominant compound in all the three tissues and its levels were positively correlated with total As concentrations. This indicates that AB greatly contributes to As accumulation in green turtles. Higher concentrations of remaining As in the sample after extraction were detected in the liver, implying that lipid-soluble or protein bound As compounds accumulate in the liver of green turtles. Total As levels in tissues showed significant negative correlations with standard carapace length. The size-dependence of As accumulation in green turtles may be related to their feeding habit, shifting from carnivore to herbivore at different growth stages. Concentrations of AB and dimethylarsinic acid (DMA) were low in the stomach contents but high in the tissues, implying bioaccumulation of these arsenicals in green turtles. (C) 2008 Elsevier Ltd. All rights reserved.
  • Kei Nakayama, Shin-Ichi Kitamura, Yasunori Murakami, Jun-Young Song, Sung-Ju Jung, Myung-Joo Oh, Hisato Iwata, Shinsuke Tanabe
    MARINE POLLUTION BULLETIN 57 6-12 445 - 452 2008年 研究論文(学術雑誌) 
    Heavy oil contamination is one of the most important environmental issues. Toxicities of polycyclic aromatic hydrocarbons (PAHs), including immune toxicities, are well characterized, however, the immune toxic effects of heavy oil, as a complex mixture of PAHs, have not been investigated. In the present study, we selected Japanese flounder (Paralichthys olivaceus) as a model organism, and observed alteration of immune function by the exposure to heavy oil. To analyze the expression profiles of immune system-related genes, we selected 309 cDNAs from our flounder EST library, and spotted them on a glass slide. Using this cDNA array, alteration of gene expression profiles was analyzed in the kidneys of flounders exposed to heavy oil. Six Japanese flounders (mean body weight: 197 g) were acclimated to laboratory conditions at 19-20 degrees C. Three fish were exposed to heavy oil C (bunker C) at a concentration of 3.8 g/L for 3 days, and the others were kept in seawater without heavy oil and used as the control. After the exposure period, the fish were transferred into control seawater and maintained for 4 days, and then they were dissected and their kidneys were removed. Total RNA was extracted from the kidney samples to use in gene expression analyses. The microarray detected alteration of immune system-related genes in the kidneys of heavy oil-exposed flounders, including down-regulation of immunoglobulin light chain, CD45, major histocompatibility complex class II antigens and macrophage colony-stimulating factor precursor, and up-regulation of interleukin-8 and lysozyme. These results suggest that pathogen resistance may be weakened in heavy oil-exposed fish, causing a subsequent bacterial infection, and then proinflammatory genes may be induced as a defensive response against the infection. Additionally, we found candidate genes for use as biomarkers of heavy oil exposure, such as N-myc downstream regulated gene 1 and heat shock cognate 71 kDa proteins. (c) 2008 Elsevier Ltd. All rights reserved.
  • Tu Binh Minh, Hisato Iwata, Shin Takahashi, Pham Hung Viet, Bui Cach Tuyen, Shinsuke Tanabe
    REVIEWS OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, VOL 193 193 213 - 290 2008年 論文集(書籍)内論文 
    Global contamination and toxic effects of persistent organic pollutants (POPs) have been an emerging environmental issue and have received considerable attention during the past four decades. Although the extent of contamination by POPs has been dominant in industrialized nations, an increasing number of recent investigations have highlighted the role of the Asia-Pacific region as a potential source of emission for these chemicals, particularly to pristine areas such as the Arctic and the Antarctic (Tanabe et al. 1994; Tanabe 2000, 2002; Tanabe and Subramanian 2006). © 2008 Springer.
  • Tu Binh Minh, Nguyen Hung Minh, Hisato Iwata, Shin Takahashi, Pham Hung Viet, Bui Cach Tuyen, Shinsuke Tanabe
    Developments in Environmental Science 7 515 - 555 2007年12月 
    This chapter provides an overview of the contamination by persistent organic pollutants (POPs) in Vietnam on the basis of the results of extensive monitoring studies conducted in our laboratory during the last two decades. Surveys conducted in the framework of Asia-Pacific Mussel Watch Program during early 1990s indicated widespread contamination by polychlorinated biphenyls (PCBs) and organochlorine (OC) insecticides, particularly DDTs and HCHs in various environmental compartments such as air, water, soils, sediments, and fish collected from different parts of Vietnam. Recent studies have revealed elevated contamination by DDTs in fish, mussels, and birds from Vietnam. Interestingly, DDT residue concentrations in fish and birds from Vietnam are among the highest values reported for the countries in Asia-Pacific region, suggesting the role of Vietnamese environment as a potential emission source of DDTs in this region. Open dumping sites for municipal wastes in some major cities such as Hanoi and Hochiminh City is a matter of concern with regard to environmental pollution, particularly contamination by dioxins (PCDDs) and related compounds such as dibenzofurans (PCDFs) and coplanar PCBs. Soils collected in dumping sites in Hanoi contained higher PCDD/F residues as compared to general soils collected far from dumping sites. PCDD/F concentrations in a few soil samples from Hanoi exceeded the environmental guideline values, suggesting potential health effects on humans and wildlife living near these dumping sites. Daily intakes of DDTs via seafood estimated for Vietnamese general population were among the highest values reported for East Asian countries. In the open dumping sites, intakes of dioxins by residents were significantly greater than those living far from dumping sites. Particularly, the estimated intakes of dioxins via soil ingestion and dermal exposure for children were higher than those for adults, suggesting greater risk of dioxin exposure for children in dumping sites. Future studies should be focused on the temporal trends of POPs in biota in Vietnam to predict the future trends of contamination and to understand possible toxic impacts on organisms. In addition, human exposure and possible toxic effects, particularly on children should be considered as priority research as they are the most susceptible group and have higher exposure levels to dioxins. © 2007 Elsevier Ltd. All rights reserved.
  • Tomoko Yasui, Eun-Young Kim, Hisato Lwata, Diana G. Franks, Sibel I. Karchner, Mark E. Hahn, Shinsuke Tanabe
    TOXICOLOGICAL SCIENCES 99 1 101 - 117 2007年09月 研究論文(学術雑誌) 
    Dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induce various toxic effects through the aryl hydrocarbon receptor (AhR) signaling pathway. Here, we investigated the structural and functional characteristics and molecular evolution of multiple AhRs in black-footed albatross (Phoebastria nigripes) an common cormorant (Phalacrocorax carbo). We report the complementary DNA sequences of two distinct AhRs, designated AhR1 and AhR2, from these species as well as the identification of an AhR2-like gene sequence from the chicken genome database. Phylogenetic analysis reveals that avian AhR1 and AhR2 are orthologous to mammalian AhR1 and fish AhR2, respectively, supporting the hypothesis that an ancestral AhR gene underwent a tandem duplication prior to the divergence of fish and tetrapod lineages. In vitro-expressed AhR1 and AhR2 isoforms from both albatross and cormorant exhibited specific binding to [H-3]TCDD, as assessed by velocity sedimentation. An in vitro reporter gene transactivation assay revealed that both AhR1 and AhR2 are transcriptionally active, but AhR2 appears to have reduced transcriptional efficacy. Hepatic messenger RNA expression level of cormorant AhR1 was greater than that of AhR2. Together, these results suggest that AhR1 is the dominant form of avian AhRs, in contrast to fish, in which AhR2 is the major form. Comparative analysis of AhR diversity and gene synteny among chicken, zebrafish, and human suggests that additional, independent duplications have occurred in the fish and tetrapod lineages following the initial tandem duplication on the ancestral chromosome. The identification and characterization of avian AhR1 and AhR2 provide new insight into the evolution of AhR structure and function in vertebrates.
  • Satoko Niimi, Eun-Young Kim, Hisato Iwata, Michio X. Watanabe, Genta Yasunaga, Yoshihiro Fujise, Shinsuke Tanabe
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY 147 4 667 - 681 2007年08月 研究論文(学術雑誌) 
    Full-length cDNA sequences of cytochrome P450 (CYP) 2C78, 2EI, 3A72, 4A35 and 4V6 isozymes were isolated from a hepatic cDNA library of common minke whale (Balaenoptera acutorostrata). The deduced amino acid sequences of minke whale CYP2C78, 2131, 3A72, 4A35 and 4V6 showed high identities with cattle CYP2C86 (83%), pig CYP2E1 (85%), sheep CYP3A24 (82%), pig CYP4A21 (80%), and human CYP4V2 (76%), respectively. To investigate whether or not these CYP expression levels are altered by contamination of organochlorine contaminants (OCs), mRNA levels of these CYPs in the liver of common minke whale were measured using a quantitative real-time RT-PCR method, and the quantified mRNA levels were employed for the statistical analysis with the residue levels of OCs including PCBs, DDTs (p,p'-DDT, p,p-DDD and p,p'-DDE), chlordanes (cis-chlordane, trans-chlordane, cis-nonachlor, trans-nonachlor and oxychlordane), HCHs (alpha, beta- and gamma-isomers) and hexachlorobenzene that have already been reported elsewhere. Spearman's rank correlation analyses showed no significant correlation between CYP expression levels and each OC level in the common minke whale liver, implying that these environmental chemicals have no potential to alter the expression levels of these CYPs or the residue levels encountered in the whale livers may not reach their transcriptional regulation levels. This suggests that the expression of individual CYPs in the whale liver may be at basal level. Relationships among hepatic mRNA expression levels of these CYP2-4 isozymes together with CYP1A1 and CYP1A2 were also examined. Significant positive correlations were detected among mRNA expression levels of individual CYP isozymes in most cases. These associations indicate that the transcriptional regulation of these CYPs examined in this study maybe reciprocally related. CYP1A1 levels showed a positive correlation with CYP1A2 levels (r=0.64,p < 0.01) indicating that both CYP isozymes were regulated by aryl hydrocarbon receptor activated by endogenous ligands. A strong positive correlation between CYP2C78 and 3A72 (r=0.90, p < 0.001) suggests that expression of these CYP isozyrnes may be under a regulation mechanism of cross-talk in which specific nuclear receptors such as constitutive androstane receptor and pregnane X receptor are involved. The present study indicates that minke whale from the North Pacific may be a model species to investigate the mechanism of basal regulation of these CYPs. (c) 2007 Elsevier Inc. All rights reserved.
  • Fujiyo Suehiro, Hiroko Mochizuki, Shinji Nakamura, Hisato Iwata, Takeshi Kobayashi, Shinsuke Tanabe, Yoshifumi Fujimori, Fumitake Nishimura, Bui Cach Tuyen, Touch Seang Tana, Satoru Suzuki
    CHEMOSPHERE 68 8 1459 - 1464 2007年07月 研究論文(学術雑誌) 
    Tributyltin (TBT) is organotin compound that is toxic to aquatic life ranging from bacteria to mammals. This study examined the concentration of TBT in sediment from and near the Mekong River and the distribution of TBT-resistant bacteria. TBT concentrations ranged from <2.4 to 2.4 ng/g (dry wt) in river sediment and <2.4-15 ng g(-1) (dry wt) in harbor sediment. Viable count of total bacteria ranged from 2.0 x 10(4) to 1.4 x 10(7) cfu/g, and counts of TBT-resistant bacteria ranged <1.0 x 10(2) to 2.5 x 10(4) cfu/g. The estimated occurrence rate of TBT-resistant bacteria ranged from <0.01 to 34% and was highest in upstream sites in Cambodia. The occurrences of TBT in the sediment and of TBT-resistant bacteria were unrelated, and chemicals other than TBT might induce TBT resistance. TBT-resistant bacteria were more abundant in the dry season than in the rainy season. Differences in the selection process of TBT-resistant bacteria between dry and rainy seasons were examined using an advection-diffusion model of a suspended solid (SS) that conveys chemicals. The estimated dilution-diffusion time over a distance of 120 km downstream from a release site was 20 days during dry season and 5 days during rainy season, suggesting that bacteria at the sediment surface could be exposed to SS for longer periods during dry season. (C) 2007 Elsevier Ltd. All rights reserved.
  • Shusaku Hirakawa, Hisato Iwata, Yoko Takeshita, Eun-Young Kim, Tomohiro Sakamoto, Yuka Okajima, Masao Amano, Nobuyuki Miyazaki, Evgeny A. Petrov, Shinsuke Tanabe
    TOXICOLOGICAL SCIENCES 97 2 318 - 335 2007年06月 研究論文(学術雑誌) 
    This study attempts to relate the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) level with certain responses including the catalytic activities and expression of hepatic cytochrome P450 (CYP) 1A and CYP1B in wild population of Baikal seal (Pusa sibirica). We isolated full-length CYP1A1, 1A2, and 1B1 cDNAs, which encode proteins of 516, 512, and 543 amino acids, respectively. Immunochemical analysis demonstrated that a cross-reactive protein with polyclonal antibody against rat CYP1A1 or CYP1B1 was detected in the seal liver. Total TEQ levels showed significant positive correlations with expression levels of CYP1A1, 1A2, and 1B1 mRNAs, and further with both CYP1A- and CYP1B-like proteins, indicating chronic induction of these CYP isozymes by TEQs. The 50% effective concentration for CYP1A-like protein induction was estimated to be 65 pg TEQ/g wet weight. To evaluate the potential of congener-specific metabolism, profiles of negative correlations between the concentrations of eachcongener normalized to a relatively recalcitrant congener, PCB169, and CYP1A-like protein levels were also estimated. Significant negative correlations of 2,3,7,8-tetrachlorodibenzofuran and PCB77 to CYP1A-like protein expression may possibly be due to the preferential metabolism of these congeners. Anti-rat CYP1A1 and CYP1B1 antisera equivalently inhibited ethoxyresorufin O-deethylase (EROD) activity in the seal microsomes, suggesting that both CYPs are involved in EROD activity. Hepatic EROD revealed an increasing trend at lower TEQs, but a declining trend at higher levels, implying a catalytic inhibition of CYP1A and CYP1B. Furthermore, ratios of CYP1B1/CYP1A1 mRNA expression levels increased with TEQs, indicating the enhanced risk of carcinogenicity by preferential induction of CYP1B1 by TEQs in the liver.
  • Tetsuro Agusa, Takashi Kunito, Hisato Iwata, In Monirith, Chhoun Chamnan, Touch Seang Tana, Annamalai Subramanian, Shinsuke Tanabe
    CHEMOSPHERE 68 3 590 - 596 2007年06月 研究論文(学術雑誌) 
    High concentration of mercury (Hg) in hair has been reported for Cambodians. To confirm the Hg contamination occurring through intake, Hg concentrations were determined in both hair and blood of residents (n = 20) from Phnom Penh, Cambodia. Mercury concentrations in the hair and blood were 0.69-190 mu g g(-1) dry wt and 5.2-58 mu g l(-1), respectively, which were lower than those from Hg contaminated or high fish intake regions, but were higher than those from non-contaminated regions. Some female subjects had hair and blood Hg levels exceeding the threshold values for neurotoxic effects. Interestingly, serum estrone and estradiol levels were positively correlated with blood Hg level for both males and females, indicating possible induction of female hormones by Hg exposure in Cambodians. (c) 2007 Elsevier Ltd. All rights reserved.
  • Sonoko Yamaguchi, Chiemi Miura, Aki Ito, Tetsuro Agusa, Hisato Iwata, Shinsuke Tanabe, Bui Cach Tuyen, Takeshi Miura
    AQUATIC TOXICOLOGY 83 1 43 - 51 2007年06月 研究論文(学術雑誌) 
    To stimate the influence of water contaminants on fish reproduction in the Mekong Delta area, we sampled cultivated male catfish (Pangasianodon hypophthalmus), investigated testicular development, and measured persistent organic pollutants (POPs) and trace element levels in muscle and liver, respectively. Various testes sizes were observed although sampling took place during a short period. Histological analysis revealed that all developmental stages of germ cells were observed in catfish with large testis, whereas only necrotic spermatogonia but no other germ cells were observed in catfish with small testis. In small testis, furthermore, vacuolization and hypertrophy of Sertoli cells were observed. Measurement of POPs in muscle and trace elements in liver demonstrated that there were negative correlations between GSI and the concentrations of Pb, Mo, Rb and As. To clarify possible direct effects of Pb, Mo, Rb and As on spermatogenesis in fish, we investigated the effects of these trace elements on spermatogenesis using in vitro testicular organ culture of Japanese eel (Anguilla japonica). Treatment with each of the trace elements alone did not affect spermatogenesis. However, treatment with 10(-7) M of Pb, 10(-5) and 10(-4) M of Mo, 10(-5) -10(-3) M of Rb or 10(-5) M of As inhibited the spermatogenesis induced by 11-ketotestosterone (11 KT). Furthermore, treatment with 10(-4) M of As in combination with 11KT caused necrosis of testicular fragments. Taken together, these results are consistent with the hypothesis that Ph, Mo, Rb and As can exert inhibitory effects on spermatogenesis in catfish inhabiting the Mekong Delta area. (C) 2007 Elsevier B.V. All rights reserved.
  • Nguyen Hung Minh, Tu Binh Minh, Hisato Iwata, Natsuko Kajiwara, Tatsuya Kunisue, Shin Takahashi, Pham Hung Viet, Bui Cach Tuyen, Shinsuke Tanabe
    ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 52 4 458 - 465 2007年05月 研究論文(学術雑誌) 
    Surficial sediment samples were collected from Hochiminh City canals, the Sai Gon-Dong Nai River, and its estuary, one of the most predominant industrial areas in Hochiminh City, southern Vietnam, for determination of selected persistent organic pollutants (POPs). Contamination pattern was as follows: PCBs >= DDTs > HCB > CHLs > HCHs. Concentrations of PCBs and DDTs ranged from 0.50-150 ng/g and 0.15-72 ng/g dry wt, respectively. On the other hand, concentrations of CHLs, HCHs, and HCB were mostly < 2 ng/g dry wt. Levels of the all organochlorines (OCs) in Hochiminh City canals were significantly higher than those in the other areas, indicating the urban areas as major pollution sources to the aquatic environment. The contamination pattern was PCBs > DDTs in the city canals but PCBs < DDTs in the downstream and the estuary, suggesting particularly high contamination by PCBs in the city. Examination of DDTs composition and their ratios demonstrated continuous input of this pesticide to the city canals. However, the combination of our data and those from available literature implies a decreasing trend of PCBs and DDTs in the environment. DDTs concentrations have been reduced 50% after approximately 5 years. Composition of CHLs in the sediment from Hochiminh City canals was comparable to those of common technical mixtures, suggesting continuous input of CHLs to the environment. CHLs might be in use for purposes like termite control, wood preservation, and protection of underground cables. Hazard assessment implies high toxic potential of DDTs for sediments from Hochiminh City canals and suggests the need for better management of municipal discharges.
  • Jin-Seon Lee, Eun-Young Kim, Hisato Iwata, Shinsuke Tanabe
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 145 3 379 - 393 2007年04月 研究論文(学術雑誌) 
    High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAHs) are accumulated in fish-eating birds including common cormorant (Phalacrocorax carbo). Most of the biochemical and toxic effects of TCDD are mediated by a basic helix-loop-helix and a conserved region among Per, ARNT, and Sim (bHLH/PAS) proteins, aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT). To study the molecular mechanism of TCDD toxicity in common cormorant as an avian model species, characterization of the AHR/ARNT signaling pathway in this species is necessary. The present study focuses on molecular characterization of ARNT from common cormorant (ccARNT). The cDNA of the ccARNT isoform, ccARNT1 obtained by the screening of hepatic cDNA library contains a 2424-bp open reading frame that encodes 807 amino acids, exhibiting high identities (92%) with chicken ARNT. This isoform contains a unique 22 amino acid residue in 3' end of PAS A domain as is also recognized in chicken ARNT. The ccARNT2 cDNA isolated from brain tissue has a 2424-bp open reading frame. The deduced amino acid sequence of ccARNT2 protein (716 aa) shows a conservation of bHLH and PAS motif in its N-terminal region with high similarities (96% and 78%, respectively) to that of ccARNT1. Using quantitative RT-PCR methods, the tissue distribution profiles of ccARNT1 and ccARNT2 were unveiled. Both ccARNT1 and ccARNT2 mRNAs were ubiquitously expressed in all examined tissues including liver. The expression profile of ccARNT1 was comparable with that of rodent ARNT1, but ccARNT2 was not with rodent ARNT2, implying different roles of ARNT2 between the two species. There was a significant positive correlation between ARNT1 and ARNT2 mRNA expression levels in the liver of wild cormorant population, indicating that their expressions may be enforced by similar transcriptional regulation mechanism. Novel variants of ccARNT1 and ccARNT2 isoforms that were supposed to arise from their splicing process were also identified and their hepatic expression profiles were determined. These results indicate that ccARNT1, ccARNT2 and their splice variants may more intricately regulate the AHR/ARNT signaling pathway and consequently may be responsible for the species diversity of toxic effects and susceptibility to PHAHs. (c) 2007 Elsevier Inc. All rights reserved.
  • Dong-Ha Nam, Eun-Young Kim, Hisato Iwata, Shinsuke Tanabe
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 145 3 295 - 305 2007年04月 研究論文(学術雑誌) 
    To characterize avian MTs, MT cDNAs were cloned from liver of cormorant (Phalacrocorax carbo) and mallard (Anas platyrhynchos). Expression profiles of NIT isoforms and relationships between metal accumulation and MT mRNA expression in tissues were also investigated. We succeeded in cDNA cloning of MT1/2 from cormorant and MT1 in mallard. DNA sequence of chicken MT1 was obtained from chicken (Gallus gallus) genomic database. Considering previous reports on avian MTs, birds possess at least two distinct MT isoforms. Comparison of genomic synteny among vertebrates and phylogenetic analysis of MT amino acid sequences revealed that avian MT 1/2 are evolutionarily close to mammalian MT3. Messenger RNAs of both MT isoforms were detected in all the tissues/organs in cormorant and mallard. Liver was the primary organ for cormorant MT1/2, and mallard MT2, whereas MT1 was dominant in mallard heart. Interspecies comparison of tissue distribution of MT mRNA expression between cormorant and mallard indicated that MT2 profile was similar, but MT1 was not. Significant positive correlations of mRNA expression levels between MT1 and MT2 were observed in the liver and kidney of cormorants, whereas no correlation was found in mallards. Expression levels of cormorant MT1/2 showed significant positive correlations with hepatic Cu and Zn concentrations, suggesting that both MT isoforms were induced by Cu and Zn in livers. Cormorant MT2 expression level exhibited a significant positive correlation with hepatic Ag, and a negative correlation with Rb, indicating that Ag and Rb concentrations depend on the expression of MT2 by Cu and Zn. In mallard, MT1 had no correlation with any metal concentration, and MT2 expression was positively correlated only with Cu, even though hepatic Cu and Zn concentrations in mallard were much higher than in cormorant. This may indicate that cormorant is a more susceptible species than mallard in terms of MT induction. These findings suggest tissue-, species-, and MT isoform-specific responses to metal stresses in these aquatic birds. (c) 2007 Elsevier Inc. All tights reserved.
  • Nguyen Hung Minh, Tu Binh Minh, Natsuko Kajiwara, Tatsuya Kunisue, Hisato Iwata, Pham Hung Viet, Nguyen Phuc Cam Tu, Bui Cach Tuyen, Shinsuke Tanabe
    CHEMOSPHERE 67 9 1794 - 1801 2007年04月 研究論文(学術雑誌) 
    The Mekong River delta is one of the largest agricultural land in the Southeast Asia. It plays a very important role for agriculture and fisheries in South Vietnam. However, comprehensive studies on the environmental pollution of persistent organic pollutants (POPs) in Mekong River delta have not been carried out in recent years. In this study, we collected sediment samples from the Mekong River to evaluate the contamination and ecological risks caused by several POP's. The contamination pattern of POPs was DDT > PCBs > CHLs > HCHs > HCB. DDTs are the most abundant pollutants, their concentration ranging from 0.01 to 110 ng/g dry wt, followed by PCBs (0.039-9.2 ng/g dry wt). DDTs and PCBs concentrations were higher in sediment from adjacent to urban areas than those from rural and agricultural sites, suggesting urban areas as important point sources of DDTs and PCBs to the river. Ratio of pp'-DDT/p,p'-DDE was lower compared to those previously reported. However, some samples still had the ratio higher than 0.5, indicating recent input of DDT into the aquatic environments. This result shows that although the magnitude of contamination decreased over time, recent inputs of DDTs to the river still occur. Some sediment samples had concentrations of DDT compounds higher than the standards from the Canadian Environmental Quality Guideline, suggesting continuous monitoring for POPs contamination in the Mekong River is necessary. (c) 2006 Elsevier Ltd. All rights reserved.
  • Kaoru Azumi, Shinli Nakamura, Shin-Ichi Kitamura, Sung-Ju Jung, Keisuke Kanehira, Hisato Iwata, Shinsuke Tanabez, Satoru Suzuki
    FISHERIES SCIENCE 73 2 263 - 269 2007年04月 研究論文(学術雑誌) 
    Recently, a serious disease spread extensively in aquaculture sites of the ascidian Halocynthia roretzi in Korea. To understand circumstances of ascidians in Korean aquaculture sites, residue levels of organotin compounds were analyzed, and detection of a marine birnavirus (MABV) in tissues of H. roretzi was attempted. Korean H. roretzi showed high concentrations of butyltins (mono, di, and tributyltins), especially in the gill, hepatopancreas, and digestive tract. However, there was no significant difference in the residues of butyltins in the hepatopancreas between diseased and non-diseased ascidians. The positive rate of MABV detection was high in the hepatopancreas, but also no significant difference was observed between diseased and non-diseased individuals. These observations suggest that an accumulation of tributyltin and a latency of MABV in H. roretzi tissues does not directly relate to the occurrence of the disease.
  • Tetsuro Agusa, Takashi Kunito, Agus Sudaryanto, In Monirith, Supawat Kan-Atireklap, Hisato Iwata, Ahmad Ismail, Joompol Sanguansin, Muswerry Muchtar, Touch Seang Tana, Shinsuke Tanabe
    ENVIRONMENTAL POLLUTION 145 3 766 - 777 2007年02月 研究論文(学術雑誌) 
    Concentrations of 20 trace elements were determined in muscle and liver of 34 species of marine fish collected from coastal areas of Cambodia, Indonesia, Malaysia and Thailand. Large regional difference was observed in the levels of trace elements in liver of one fish family (Carangidae): the highest mean concentration was observed in fish from the Malaysian coastal waters for V, Cr, Zn, Pb and Bi and those from the Java Sea side of Indonesia for Sn and Hg. To assess the health risk to the Southeast Asian populations from consumption of fish, intake rates of trace elements were estimated. Some marine fish showed Hg levels higher than the guideline values by U.S. Environmental Protection Agency and Joint FAO/WHO Expert Committee on Food Additives (JECFA). This suggests that consumption of these fish may be hazardous to the people. (c) 2006 Elsevier Ltd. All rights reserved.
  • Overview of arsenic contamination in groundwater and human health in Vietnam.
    Agusa, T, Inoue, S, Kunito, T, Minh, T.B., Tu, N.P.C, Ha, N.N, Trang, P.T.K, Subramanian, A, Iwata, H, Viet, P.H, Tuyen, B.C, Tanabe, S
    Annual Report of FY 2006, The Core University Program between Japan Society for the Promotion of Science (JSPS) and Vietnamese Academy of Science and Technology (VAST) 89-92  2007年
  • Arsenic pollution in groundwater in the lower Mekong Basin.
    Inoue, S, Agusa, T, Kubota, R, Kunito, T, Minh, T.B, Trang, P.T.K, Viet, P.H., Tu, N.P.C, Tuyen, B.C, Reungsang, A, Srisuk, K, Nakamura, S, Takizawa, S, Chamnan, C, Tana, T.S, Iwata, H, Tanabe, S
    Chemical Pollution and Environmental Changes (Frontiers Science Series No. 48). Universal Academy Press, Tokyo. 217-220  2007年
  • Preliminary study on Hg-Se binding proteins in liver of northern fur seals.
    Ikemoto, T, Kim, E.-Y, Kunito, T, Iwata, H, Tanabe, S
    Chemical Pollution and Environmental Changes (Frontiers Science Series No. 48). Universal Academy Press, Tokyo. 205-208  2007年
  • Arsenic contamination in groundwater and residents from Vietnam, Cambodia and India.
    Agusa, T, Inoue, S, Kunito, T, Ramu, K, Charaborty, P, Chamnan, C, Trang, P.T.K, Minh, T.B, Iwata, H, Subramanian, A, Viet, P.H, Tana, T.S, Tanabe, S
    Chemical Pollution and Environmental Changes (Frontiers Science Series No. 48). Universal Academy Press, Tokyo. 55-58  2007年
  • Hisato Iwata, Eun-Young Kim, Masanobu Yamauchi, Suguru Inoue, Tetsuro Agusa, Shinsuke Tanabe
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN 127 3 417 - 428 2007年 
    The 21st Century's Center of Excellence (COE) Program "Coastal Marine Environmental Research" in Ehime University, funded by the Ministry of Education, Culture, Sports, Science and Technology, Government of Japan, started its activities in October 2002. One of the core projects of the COE Program in Ehime University is "studies on environmental behavior of hazardous chemicals and their toxic effects on wildlife". This core project deals with studies of the local and global distribution of environmental contaminants in aquatic ecosystems, retrospective analysis of such chemicals, their toxicokinetics in humans and wildlife, molecular mechanisms to determine species-specific reactions, and sensitivity of chemically induced effects, and with the development of methodology for risk assessment for the conservation of ecological and species diversity. This presentation describes our recent achievements of this project, including research on contamination by arsenic and organohalogen pollutants in the Mekong River basin and molecular mechanisms of morphologic deformities in dioxin-exposed red seabream (Pagrus major) embryos. We established the Environmental Specimen Bank (es-BANK) in Ehime University in 2004, archiving approximately 100000 cryogenic samples containing tissues of wildlife and humans that have been collected for the past 40 years. The CMES homepage offers details of samples through online database retrieval. The es-BANK facility was in operation by the end of 2005.
  • Masanobu Yamauchi, Eun-Young Kim, Hisato Iwata, Yasuhiro Shima, Shinsuke Tanabe
    AQUATIC TOXICOLOGY 80 2 166 - 179 2006年11月 研究論文(学術雑誌) 
    The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is mainly mediated by the aryl hydrocarbon receptor (AHR), which regulates the multiple target genes including cytochrome P4501A (CYP1A). In general, bony fishes, which possess at least two distinct AHRs are one of the most sensitive vertebrates to TCDD in early life stage. However, the physiological and toxicological roles of piscine multiple AHRs are not fully understood, especially in marine fish. To understand which AHR is responsible for TCDD toxicity in a marine fish species, we characterized the early life stage toxicity related to the expression of AHRs and CYP1A in red seabream (Pagrus major). The embryos at 10 h post-fertilization (hpf) were treated with 0-100 mu g/L TCDD for 80 min waterborne exposure. TCDD dose-dependently elicited developmental toxicities including mortality, yolk sac edema, retarded body growth, spinal deformity, reduced heart rate, shortened snout, underdeveloped fin, heart, and lower jaw. Intriguingly, hemorrage and pericardium edema, typical TCDD developmental defects noticed in other fish species, were not found in red seabream until test termination. The ECegg 50s for yolk sac edema, underdeveloped fin, and spinal deformity were 170, 240, and 340 pg/g, respectively. The LC(egg)50 was 360pg/g embryo, indicating that this species is one of the most sensitive fishes to TCDD toxicity. The expression levels of rsAHR1, rsAHR2 and CYP1A mRNAs were also determined in different developmental stages. The rsAHR2 mRNA expression dose-dependently increased following TCDD exposure, while rsAHR1 mRNA level was not altered. Level of rsAHR2 mRNA measured by two-step real-time PCR was 30 times higher than rsAHR1 in embryos treated with the highest dose. Temporal patterns of rsAHR2 and CYP1A mRNAs were similar in TCDD-treated embryos, representing a significant positive correlation between rsAHR2 and CYP1A mRNA levels, but not between rsAHR1 and CYP1A. In comparison of temporal trends of TCDD-induced AHRs and CYP1A expression, and developmental toxicities, the highest expression of rsAHR2 and CYP1A mRNA were detected prior to the appearance of maximal incidence of TCDD toxic manifestations. These results suggest that rsAHR2 may be dominantly involved in the transcriptional regulation of CYP1A, and several TCDD defects are dependent on the alteration of rsAHR2 and/or rsAHR2-CYP1A signaling pathway that is controlled through their expression levels. (c) 2006 Published by Elsevier B.V.
  • Hiroki Sakai, Hisato Iwata, Eun-Young Kim, Oyuna Tsydenova, Nobuyuki Miyazaki, Evgeny A. Petrov, Valeriy B. Batoev, Shinsuke Tanabe
    TOXICOLOGICAL SCIENCES 94 1 57 - 70 2006年11月 研究論文(学術雑誌) 
    To characterize the function of constitutive active/androstane receptor (CAR) in aquatic mammals, CAR complementary DNA (cDNA) was cloned from the liver of Baikal seal (Pusa sibirica) from Lake Baikal, Russia, and the messenger RNA (mRNA) expression levels in various tissues/organs of the wild population and the CAR ligand profiles were investigated. The seal CAR cDNA had an open reading frame of 1047 bp encoding 348 amino acids that revealed 74-84% amino acid identities with CARs from rodents and human. The mRNA expression profile of tissues/organs represented that Baikal seal CAR was predominantly expressed in the liver followed by heart and intestine. The expression analysis of hepatic CAR mRNA showed no correlation with expression of cytochrome P450 (CYP) 1A, 1B, 2B, 2C, and 3A-like proteins, indicating that the CAR expression level may not be the sole determinant of the regulation of these CYP expressions in the seal liver. There was no significant correlation between CAR expression and any of the persistent organic pollutants (POPs) levels. Furthermore, we performed an in vitro CAR transactivation assay using MCF-7 cells transfected with Baikal seal CAR expression plasmid and (NR1)(3)-luciferase reporter gene plasmid. In the transactivation analysis of Baikal seal CAR, neither repression by androstanol and androstenol, nor activation by estrone and estradiol, which are recognized as endogenous ligands for mouse and human CARs, was detected. On the other hand, bile acids such as chenodeoxycholic acid, deoxycholic acid, and lithocholic acid activated the seal CAR as well as mouse CAR. As for exogenous chemicals, the seal CAR was transactivated by a human CAR agonist, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime), but not by a mouse CAR agonist, (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene). In addition, the seal CAR was also activated by polychlorinated biphenyls (PCBs) (Kanechlor-500, International Union of Pure and Applied Chemistry No. PCB153; 2,2',4,4',5,5'-hexachlorobiphenyl and PCB180; 2,2',3,4,4',5,5'-heptachlorobiphenyl), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE). The seal CAR responded more sensitively to PCBs than the mouse CAR. Based on the results of CAR transactivation assay, the lowest observable effect levels of Kanechlor-500, PCB153, PCB180, p,p'-DDT, and p,p'-DDE in Baikal seal were estimated to be 10, 20, 20, 10, and 10 ppm on wet weight basis, respectively. These results suggest that CAR is conserved in diverse mammalian species including seals. Whereas the seal CAR-mediated gene transcription may potentially be a sensitive response to the exposure of certain POPs, the ligand profile of seal CAR may be different from those of other mammalian CARs. This study indicates that CAR-mediated responses may be useful information to assess the ecotoxicological risk of xenobiotics such as POPs in wildlife but the previous results derived from rodent and human CAR may not be applicable to the risk assessment in wild species.
  • Nguyen Hung Minh, Tu Binh Minh, Natsuko Kajiwara, Tatsuya Kunisue, Hisato Iwata, Pham Hung Viet, Nguyen Phuc Cam Tu, Bui Cach Tuyen, Shinsuke Tanabet
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 25 10 2700 - 2708 2006年10月 研究論文(学術雑誌) 
    Commercial feeds for aquaculture and catfish samples were collected from the Mekong River Delta, Vietnam, for determination of polybrominated diphenyl ethers (PBDEs) and selected persistent organochlorines, including polychlorinated bi-phenyls (PCBs), DDT and its metabolites (DDTs), chlordane-related compounds (CHLs), hexachlorocyclohexane isomers (HCHs), and hexachlorobenzene (HCB). The most abundant contaminants were DDTs, with concentrations ranging from 10 to 700 ng/g lipid weight, followed by PCBs (1.0-80 ng/g), CHLs (< 0.01-8.2 ng/g), PBDEs (0.12-3.7 ng/g), HCHs (< 0.03-5.1 ng/g), and HCB (< 0.07-3.2 ng/g). Polybrominated diphenyl ethers were detected in all samples, suggesting their widespread contamination in the region. However, PBDE contamination levels in the present catfish specimens were low in comparison to levels worldwide. Interestingly, residue levels of all the contaminants were significantly higher in catfish collected near a municipal dumping site compared to farmed catfish. This suggests that runoffs from the dumping site during floods and rains may have brought pollutants to the surrounding areas. Contamination pattern in aquaculture feeds revealed elevated levels of PCBs and PBDEs in samples from foreign companies, perhaps implying their higher residues in some imported ingredients. Congener profiles of PBDEs and PCBs demonstrated similarity between the farmed catfish and the aquaculture feeds, suggesting these feeds as a major source of pollution to the farmed catfish. On the other hand, the PBDE and PCB profiles in the dumpsite catfish are clearly different from those of the farmed catfish, revealing their exposure to different sources. Risk assessment showed significantly higher intake of the contaminants by people who eat catfish cultured near the dumping areas. Further investigation regarding fate and occurrence of the contaminants in dumping sites is necessary.
  • Akira Kubota, Hisato Iwata, Heather M. H. Goldstone, Eun-Young Kim, John J. Stegeman, Shinsuke Tanabe
    TOXICOLOGICAL SCIENCES 92 2 394 - 408 2006年08月 研究論文(学術雑誌) 
    The present study characterized cytochrome P4501A (CYP1A) isoforms from common cormorant (Phalacrocorax carbo) with regard to their evolutionary relationships and their roles in disposition of dioxin and related compounds (DRCs). Two clones isolated from a cormorant liver cDNA library were named CYP1A4 and CYP1A5 on the basis of greatest overall amino acid identity shared with chicken (Gallus gallus) CYP1A4 (78%) and CYP1A5 (78%), respectively. Spatial heterogeneity in phylogenetic signal along the sequences strongly indicated that cormorant CYP1A4 and CYP1A5 have undergone partial interparalog gene conversion, similar to chicken and mammalian CYP1As. Phylogenetic analysis of a putatively unconverted region produced a tree topology consistent with the orthology of avian CYP1A5s with mammalian CYP1A2s and avian CYP1A4s with mammalian CYP1A1s. Hepatic CYP1A4 and CYP1A5 mRNA levels in wild cormorants from Lake Biwa, Japan, were quantified to examine the effects of DRCs on isoform-specific expression and to evaluate the toxicokinetics of DRCs in which CYP1A expression is involved. Both CYP1A4 and CYP1A5 mRNA levels were positively correlated with total tetrachlorodibenzo-p-dioxin toxic equivalents and concentrations of each congener in most cases in the liver, suggesting the induction of both enzymes through a shared transcriptional mechanism. The lack of correlation of 2,3,7,8-tetrachlorodibenzofuran and 3,3',4,4'-tetrachlorobiphenyl (PCB77) to CYP1A gene expression is likely due to the rapid metabolism of these two congeners. Liver-to-muscle concentration ratios for most DRC congeners except PCB77 and mono-ortho coplanar polychlorinated biphenyls significantly increased with an elevation of CYP1A4 and CYP1A5 mRNA levels. The present data suggest that hepatic sequestration of some DRCs occurs in cormorant via binding to either CYP1A5 or both CYP1A4 and CYP1A5.
  • T. B. Minh, M. Watanabe, N. Kajiwara, H. Iwata, S. Takahashi, A. Subramanian, S. Tanabe, S. Watanabe, T. Yamada, J. Hata
    ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 51 2 296 - 313 2006年08月 研究論文(学術雑誌) 
    Concentrations of persistent organochlorines (OCs)-such as polychlorinated biphenyls (PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene, and tris(4-chlorophenyl)methane [TCPMe]-were determined in plasma samples from residents of three sub-metropolitan locations in Japan (Miyako, Saku, and Tottori) for the purpose of studying the geographic variation and specific accumulation of OCs. Residue concentrations of PCBs and DDTs were the highest in samples collected in Saku (400 and 370 ng/g lipid wt, respectively) whereas samples from Miyako contained greater CHL residues (70 ng/g lipid wt) than those from the other two locations. This contamination pattern reflects the historic use of OCs in each area. For the first time, tris (4-chlorophenyl) methane (TCPMe) concentrations were detected in most of the plasma sample analyzed. Concentrations of TCPMe which ranged from < 0.1 to 8.1 ng/g lipid wt eight, were lower than those previouly reported in other human tissue. Larger geographic differences in OC accumulation were observed for PCBs and CHLs, whereas DDTs and HCHs exhibited little variability. PCB concentrations in samples from Saku residents were higher than those from residents of countries in the circumpolar Arctic region but lower than those reported for some populations in the United States and Western European countries. Interestingly, CHL residue concentrations in human blood from Japan are among the highest values reported for the countries examined, suggesting continued increased exposure to CHLs of the Japanese population. Time-trend analysis of CHLs in human blood samples from Miyako (Okinawa prefecture) showed that CHL residues have decreased substantially during the last decade, indicating the effect of the official ban of CHLs in 1986 in Japan. Isomer-specific analysis of PCBs revealed lower proportions of higher chlorinated congeners such as hepta- and octachlorobiphenyls in women than in men, suggesting the possibility of preferential elimination of higher chlorinated biphenyls in women. The difference in sex-dependent accumulation of OC compounds in healthy and ill persons was suggested. To our knowledge, this is the first report on the specific accumulation of persistent QCs, including TCPMe, in human blood samples from Japan.
  • NH Minh, TB Minh, N Kajiwara, T Kunisue, A Subramanian, H Iwata, TS Tana, R Baburajendran, S Karuppiah, PH Viet, BC Tuyen, S Tanabe
    ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 50 4 474 - 481 2006年05月 研究論文(学術雑誌) 
    In Asian developing countries, large amounts of municipal wastes are dumped daily in open dumping sites without proper management. This practice may cause several adverse environmental consequences and increased health risk to local communities. To elucidate contamination by persistent organic pollutants (POPs)-including dichloro-diphenyl-trichloroethane and its metabolites (DDTs), hexachlorocyclohexanes (HCHs), chlordanes, hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs)-in such dumping sites, soil samples were collected from open dumping sites and respective control sites in Cambodia, India, and Vietnam from 1999 through 2001. Our results demonstrated that DDTs, PCBs, and HCHs were dominant contaminants in the dumping sites. However, the contamination pattern was not consistent, showing higher HCHs in India than in Cambodia and Vietnam. Interestingly, in all of the countries, extremely higher levels of POPs were observed in the dumping sites compared with those in the respective control sites, suggesting significant amplification of POP contamination in the dumping sites of Asian developing countries. Mean concentrations of DDTs and PCBs were 350 and 140 ng/g dry weight, respectively, in the dumping sites of Cambodia and 26 and 210 ng/g, respectively, in India. These residue levels were hundreds to thousands times higher than those in general soils, implying possible risk to human health of the local communities, especially to the rag pickers, including children who work in these sites to collect recyclable materials. Composition of DDT compounds suggested their recent use in populated areas, which in turn might have caused increased levels of DDTs in the open dumping sites. In addition, composition of HCH isomers revealed their different use pattern in different countries.
  • Akira Kubota, Hisato Iwata, Shinsuke Tanabe, Kumiko Yoneda, Sachiko Tobata
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 25 4 1007 - 1016 2006年04月 研究論文(学術雑誌) 
    Concentrations of dioxins and related compounds (DRCs), such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated bipherryls (Co-PCBs), were determined in black-eared kites (BEKs; Milvus migrans) collected from the Kanto district in Japan. Total 2,3,7,8-tetra-CDD toxic equivalents (TEQs) were in the range of 99 to 3,800 pg/g lipid weight in the liver and 42 to 760 pg/g lipid weight in the pectoral muscle. Three congeners, including PCB 126, 2,3,4,7,8-penta-CDF, and 1,2,3,7,8-penta-CDD, made a greater contribution to total TEQs in both tissues. Levels of ethoxyresorufi n-O-deethy lase activity and a cross-reactive protein with anti-rat cytochrome P4501 A (CYPIA) polyclonal antibodies showed no significant correlation with hepatic TEQs. This may be attributed to low sensitivity and insufficient TEQ levels to cause CYPIA induction, high metabolic potential of a series of congeners, and influence of CYPIA inducers other than DRCs. Most of the PCDD/ Fs and non-ortho Co-PCBs exhibited a total TEQ- and CYPIA-dependent increase in the liver to muscle concentration ratios, implying their concentration-dependent hepatic sequestration in which CYPIA was involved. Comparison of the toxicokinetics in avian species revealed that BEKs possibly have higher potentials than common cormorants for metabolizing and sequestering certain congeners in the liver in terms of hepatic concentration profiles and liver:muscle concentration ratios, respectively. These results clearly indicate that the toxicokinetics of DRCs is congener-, tissue-, and species-specific as well as concentration-dependent. Therefore, CYPIA expression is one of the critical factors that determine the toxicokinetics in wild avian species.
  • T Kunisue, MX Watanabe, H Iwata, T Tsubota, F Yamada, M Yasuda, S Tanabe
    ENVIRONMENTAL POLLUTION 140 3 525 - 535 2006年04月 研究論文(学術雑誌) 
    The present study determined the contamination levels and congener-specific accumulation features of dioxins and related compounds (DRCs) in wild terrestrial mammals such as large Japanese field mice (LJFM), lesser Japanese moles (LJMs), and raccoon dogs (RDs) collected from Kanto region in Japan during 2001. The toxic equivalent quantity (TEQ) levels in the carcasses or adipose tissues were in the order of RDs >= LJMs > LJFM. Comparison of DRC congener profiles in the three species and principal component analysis (PCA) demonstrated a higher contribution of OCIDD, T(4)CB77, and P(5)CB118 in LJMs. Analysis of liver-adipose distribution of DRC congeners in RDs showed that livers contained significantly higher TEQs than adipose tissues, indicating that liver is a depository organ and critical for determining the toxicokinetics of DRCs. As for most T-4, P-5, H6CDD/DFs and for P(5)CB126, H(6)CB169 and mono-ortho PCB congeners, their liver/adipose concentration ratios in RDs revealed a tendency to increase with hepatic TEQ levels, suggesting TEQ-dependent hepatic sequestration. (c) 2005 Elsevier Ltd. All rights reserved.
  • R Kubota, T Kunito, T Agusa, J Fujihara, Monirith, I, H Iwata, A Subramanian, TS Tana, S Tanabe
    JOURNAL OF ENVIRONMENTAL MONITORING 8 2 293 - 299 2006年02月 研究論文(学術雑誌) 
    Arsenic concentrations in hair and urine, and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were examined for inhabitants of the Mekong Basin in Kratie Province, Cambodia. Also, the arsenic levels of tube-well water were determined. Total arsenic concentrations in tube-well water ranged from < I to 886 mu g L-1, and 44.8% of these exceeded the WHO drinking water guideline of 10 mu g L-1. Elevated levels of arsenic were observed in the human hair and urine, and also a significant positive correlation was observed between the concentrations in hair and urine. These results suggest that the inhabitants are chronically exposed to arsenic through drinking the tube-well water. Levels of urinary 8-OHdG were higher for the subjects with higher arsenic levels in hair and urine, suggesting that induction of oxidative DNA damage was caused by chronic exposure to arsenic in tube-well water for the inhabitants in Kratie Province. To our knowledge, this is the first report on the oxidative DNA damage caused by chronic exposure to arsenic in groundwater for the inhabitants in Cambodia.
  • K Nakayama, H Iwata, EY Kim, K Tashiro, S Tanabe
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 40 3 1076 - 1083 2006年02月 研究論文(学術雑誌) 
    To establish a monitoring system for gene expression profiles related to chemical contamination in wild common cormorants (Phalacrocorax carbo), the present study constructed an oligo array designed from expressed sequence tag (EST) sequences of the cormorant liver, where 1061 unique oligonucleotides were spotted. Common cormorants were collected from Lake Biwa, Japan in May 2001 and 2002. With the use of this oligo array, gene expression profiles in the liver of individual specimens were evaluated. To determine the expression patterns of genes altered by environmental contaminants, relationships between concentrations of persistent organochlorines including polychlorinated dibenzo-p-dioxins, furans, polychlorinated biphenyls, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane and its metabolites (DOTS), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), butyltins, and bisphenol A (BPA) and expression levels of each gene in the cormorant liver were examined using stepwise multiple regression analysis. The reliability of data obtained by the oligo array was further confirmed by quantifying the expression levels of certain genes using real-time RTPCR. The 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) level was positively correlated with both cytochrome P4501A4 and 1A5 gene expression. In addition, the mRNA level of an antioxidant enzyme, Cu/Zn superoxide dismutase, was negatively correlated with hepatic total TEQ. Other antioxidant enzymes, glutathione peroxidase 3 and glutathione S-transferase class mu, were negatively correlated with HCHs and BPA levels, respectively. The mRNA expression level of a nonenzymatic antioxidant, haptoglobin, was negatively but not significantly correlated with CHLs. These results led to a hypothesis that wild cormorant population may suffer from oxidative stress due to chemically induced formation of reactive oxygen species and subsequent reduction of antioxidant resistance. Thus, the cormorant oligo array may be a useful monitoring tool to identify specific gene expression profiles altered by various environmental contaminants. Although further research is required to clarify a definitive cause-and-effect relationship, the current study provides valuable information on contaminant-responsive genes to predict potential effects on wildlife in a real environment.
  • Arsenic contamination in groundwater and residents from Ha Nam and Ha Tay Provinces of Red River Delta, Vietnam.
    Agusa, T, Kunito, T, Inoue, S, Minh, T.B, Trang, P.T.K, Subramanian, A, Iwata, H, Viet, P.H, Tanabe, S
    Annual Report of FY 2005, The Core University Program between Japan Society for the Promotion of Science (JSPS) and Vietnamese Academy of Science and Technology (VAST). 33-36  2006年
  • T Agusa, T Kunito, J Fujihara, R Kubota, TB Minh, PTK Trang, H Iwata, A Subramanian, PH Viet, S Tanabe
    ENVIRONMENTAL POLLUTION 139 1 95 - 106 2006年01月 研究論文(学術雑誌) 
    Concentrations of As and other trace elements and their association were examined in groundwater (n=25) and human hair (n=59) collected at Gia Lam District and Thanh Tri District, suburban areas of Hanoi, Vietnam, in September 2001. Concentrations of As in the groundwater ranged from < 0.10 to 330 mu g/l, with about 40% of these exceeding WHO drinking water guideline of 10 mu g/l. Also, 76% and 12% of groundwater samples had higher concentrations of Mn and Ba than WHO drinking water guidelines, respectively. Arsenic concentrations in hair of residents in Gia Lam and Thanh Tri Districts (range 0.088-2.77 mu g/g dry wt.) were lower than those in other As-contaminated areas of the world, but were higher than those of people in noncontaminated areas. Concentrations of As and Mn in hair of some individuals from the Gia Lam and Thanh Tri Districts exceeded the level associated with their toxicity and, therefore, a potential health risk of As and Mn is a concern for the people consuming the contaminated water in this area. Cumulative As exposure was estimated to be lower than the threshold levels at the present, which might explain the absence of manifestations of chronic As poisoning and arsenicosis in the residents of Gia Lam and Thanh Tri Districts. To our knowledge, this study revealed for the first time that the residents are exposed not only to As but also Mn and Ba from groundwater in the Red River Delta, Vietnam. (c) 2005 Elsevier Ltd. All rights reserved.
  • A Sudaryanto, T Kunisue, N Kajiwara, H Iwata, TA Adibroto, P Hartono, S Tanabe
    ENVIRONMENTAL POLLUTION 139 1 107 - 117 2006年01月 研究論文(学術雑誌) 
    This study determined concentrations of polychlorinated biphenyls (PCBs) and organochlorine compound (OC) pesticides in the milk samples of women from the general population in four locations of Indonesia. The most prevalent residues of OCs were DDTs, PCBs and hexachlorocyclohexane isomers (HCHs), whereas other OCs such as chlordane compounds (CHLs), tris(4-chlorophenyl)methane and hexachlorobenzene were lower. The levels of OCs varied between locations and individuals, with DDTs higher in suburban and rural areas than urban localities, may be due to the differences in food habits and sources between the individuals and locations. Data from Purwakarta site indicated continuing DDT exposure, which may confirm recent usage of DDT in Indonesia. A positive correlation was observed between concentration of OCs in human milk and age of mothers, primiparas women having higher OCs than multiparas, suggesting these parameters play an important role influencing the OC burdens in lactating women. Some individuals accumulated DDTs and HCHs in breast milk close to or even higher than the TDI (tolerable daily intake) guidelines proposed by Health Canada. (c) 2005 Elsevier Ltd. All rights reserved.
  • MX Watanabe, H Iwata, M Okamoto, EY Kim, K Yoneda, T Hashimoto, S Tanabe
    TOXICOLOGICAL SCIENCES 88 2 384 - 399 2005年12月 研究論文(学術雑誌) 
    This study presents concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxin-like coplanar PCBs (Co-PCBs) in the liver and breast muscle of jungle crows (JCs; Corvus macrorhynchos) collected from Tokyo, Japan. 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) derived by WHO bird-TEF were in the range of 23 to 280 pg/g (lipid) in the liver, which are lower or comparable to the lowest-observed-effect-level of CYP induction in chicken, and 5.6-78 pg/g (lipid) in the pectoral muscle. Cytochrome P450 (CYP) 1A-, 2B-, 2C-, and 3A-like proteins were detected using anti-rat CYP polyclonal antibodies in hepatic microsomal fractions. Significant (p < 0.05) positive correlations between hepatic TEQs and CYP1A or CYP3A-like protein expression levels were noticed, implying induction of these CYP isozymes by TEQs. On the other hand, there was no significant positive correlation between muscle TEQ and any one of analyzed CYP isozyme expression levels. CYP1A- and CYP3A-like protein expression levels represented better correlations with pentoxy- and benzyloxyresorufin-O-dealkylase activities rather than methoxy- and ethoxyresorufin-O-dealkylase activities, indicating unique catalytic functions of these CYPs in JCs. Furthermore, we succeeded in isolating CYP1A5 cDNA from the liver of JC, having an open reading frame of 531 amino acid residues with a predicted molecular mass of 60.3 kDa. JC CYP1A5 mRNA expression measured by real-time RT-PCR had a significant positive correlation with hepatic TEQs, suggesting induction of CYP1A5 at the transcriptional level. Ratios of several Co-PCB congeners to CB-169 in the liver of JCs revealed significant negative correlations with CYP1A protein or CYP1A5 mRNA expression levels, implying metabolism of these congeners by the induced CYP1A. The liver/breast muscle concentration (L/M) ratios of PCDDs/DFs and CB-169 increased with an increase in hepatic CYP1A protein or CYP1A5 mRNA expression levels, suggesting congener-specific hepatic sequestrations by the induced CYP1A. The present study provides insights into the propensity of CYP1A induction to the exposure of dioxin-like chemicals, and unique metabolic and sequestration capacities of CYP1A in JC.
  • EY Kim, H Iwata, T Suda, S Tanabe, M Amano, N Miyazaki, EA Petrov
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 141 3 281 - 291 2005年07月 研究論文(学術雑誌) 
    Most toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAHs) are mediated by ligand-activated aryl hydrocarbon receptor (AHR) signaling pathway. To understand the regulation mechanism of AHR and AHR nuclear translocator (ARNT) expression in wild Baikal seal (Pusa sibirica) population contaminated by PHAHs, the present study investigated hepatic mRNA expression levels of AHR and its heterodimer, ARNT genes, in association with biological index (age, gender and body weight), PHAH accumulation and expression levels of cytochrome P450 (CYP) 1A and 1B. While there was no gender difference, the AHR mRNA expression levels were increased with ages (p =0.014) and body weights (p=0.015), indicating that AHR expression might be affected by these biological factors. The AHR mRNA expression levels exhibited significant positive correlations with total TEQs and most of individual congener TEQs derived from polychorinated dibenzo-p-dioxins, dibenzofurans and non-ortho coplanar polychorinated biphenyls (PCBs), indicating the transcriptional up-regulation of AHR expression by these congeners. On the other hand, there was no significant correlation between individual TEQs from mono-ortho coplanar PCBs and AHR expression. These results imply the structure-related transcriptional activity of AHR among PHAHs congeners. AHR mRNA levels showed positive correlations with both CYP1A protein (p=0.039) and CYP1A1 mRNA expression levels (p=0.046). In contrast to AHR expression, neither the total nor individual congener TEQs influenced ARNT at the transcriptional level. ARNT mRNA showed significant negative correlations with CYP1A/1B protein (p = 0.027 and p = 0.006) and CYP1A1 mRNA expression levels (p = 0.039), implying the existence of different transcriptional regulation between AHR and ARNT genes and negative regulation by CYP1A/1B-mediated signaling pathways. The present findings may render significant insight on the basic mechanisms underlying regulation of AHR and ARNT expressions associated with biological factors and PHAH exposure in wild mammalian populations. (C) 2005 Elsevier Inc. All rights reserved.
  • M Yamauchi, EY Kim, H Iwata, S Tanabe
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 141 2 177 - 187 2005年06月 研究論文(学術雑誌) 
    The aryl hydrocarbon receptor (AHR) mediates the toxic effects of planar halogenated aromatic hydrocarbons (PHAHs). Bony fishes exposed to PHAHs exhibit a wide range of developmental defects. However, functional roles of fish AHR are not yet fully understood, compared with those of mammalian AHRs. To investigate the potential sensitivity to PHAHs toxic effects, an AHR cDNA was initially cloned and sequenced from red seabream (Pagrus major), an important fishery resource in Japan. The present study succeeded in identifying two highly divergent red seabream AHR cDNA clones, which shared only 32% identity in full-length amino acid sequence. The phylogenetic analysis revealed that one belonged to AHR1 clade (rsAHR1) and another to AHR2 clade (rsAHR2). The rsAHR1 encoded a 846-residue protein with a predicted molecular mass of 93.2 kDa, and 990 amino acids and 108.9 kDa encoded rsAHR2. In the N-terminal half, both rsAHR genes included bHLH and PAS domains, which participate in ligand binding, AHR/ARNT dimerization and DNA binding. The C-terminal half, which is responsible for transactivation, was poorly conserved between rsAHRs. Quantitative analyses of both rsAHRs mRNAs revealed that their tissue expression profiles were isoform-specific; rsAHR1 mRNA expressed primarily in brain, heart, ovary and spleen, while rsAHR2 mRNA was observed in all tissues examined, indicating distinct roles of each rsAHR. Furthermore, there appeared to be species-differences in the tissue expression profiles of AHR isoforms between red seabream and other fish. These results suggest that there are isoform- and species-specific functions in piscine AHRs. (c) 2005 Elsevier Inc. All rights reserved.
  • MX Watanabe, H Iwata, M Watanabe, S Tanabe, A Subramanian, K Yoneda, T Hashimoto
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 39 12 4421 - 4430 2005年06月 研究論文(学術雑誌) 
    To assess the significance of waste dumping sites as a source of chemical contamination to ecosystems, we analyzed the residue levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and other organochlorines in the breast muscle of crows from a dumping site in the south of Chennai city, South India. Crows from the dumping site contained significantly higher total TEGs (60 +/- 27 pg/g lipid wt) than those from the reference sites (26 +/- 18 pg/g lipid wt). Especially, certain dioxin-like coplanar PCB congeners (Co-PCBs), such as CB-77 and CB-105, whose source iscommercial PCBs,were significantly higher in crows from the dumping site than those from the reference sites. Profiles of PCDDs/DFs and Co-PCBs in crows from the dumping site were similar to those of soil at the same site, which was confirmed by principal component analysis. Furthermore, significant positive correlations were obtained between the congener-specific bioconcentration factors (BCFs) of PCDDs/DFs estimated from concentrations in crows and soil from the dumping site and the theoretical BCFs calculated from water-particle and lipid-water partitioning coefficients. On the other hand, the estimated BCFs had significant negative correlations with the molecular weight of PCDDs/DFs, indicating that molecular size limits their bioaccumulation. These results suggest that dioxin-like congeners in the soil of the dumping site were transferred directly to the crows through the ingestion of on-site garbage contaminated with soil, ratherthan through trophic transfer in the ecosystem. The present study provides insight into the ecological impacts of dumping sites.
  • A Kubota, H Iwata, S Tanabe, K Yoneda, S Tobata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 39 10 3611 - 3619 2005年05月 研究論文(学術雑誌) 
    The present study examines the effects of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) on hepatic cytochromes P450 (CYP) in the wild population of common cormorants from Lake Biwa, Japan, and discusses functional roles of CYP1A in terms of correlation analysis between tissue concentrations of individual congeners and expression levels of CYP1A. Levels of alkoxyresorufin (methoxy-, ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase activities and a protein cross-reacted with anti-rat CYP1A1 polyclonal antibodies showed significant positive correlations with total 2,3,7,8-tetra chlorodibenzo-p-dioxin toxic equivalents (TEQs) or TEQs for most individual congeners in the liver of cormorants, suggesting induction of CYP1A-like protein by these chemicals. In contrast, TEQs for lower chlorinated congeners, 2,3,7,8-T4CDF and PCB77, showed relatively low correlations with the expression level of CYP1A-like protein. Concentrations of 2,3,7,8-T4CDF and PCB77 normalized to a relatively recalcitrant congener, PCB169, were negatively correlated with the CYP1A-like protein level. These results indicate preferential metabolism of those congeners by CYP1A-like protein that was induced by TEQs. Concentration ratios of liver to pectoral muscle for certain congeners significantly increased with an elevation of the CYP1A-like protein level. Comparing the results in the present study with those of previous studies using rodents treated with certain dioxin-like congeners, these congeners in the liver may be sequestered by CYP1A. Levels of cross-reactive proteins with anti-rat CYP2B1, CYP2C6, and CYP3A2 polyclonal antibodies correlated with neither TEQs nor liver/muscle concentration ratios of congeners. We conclude that the potential for CYP1A induction, and metabolism and sequestration of dioxin-like compounds by CYP1A, may be a critical factor for assessing the ecological risk in wild avian species.
  • M Kobayashi, Y Kashida, K Yoneda, H Iwata, M Watanabe, S Tanabe, H Fukatsu, N Machida, K Mitsumori
    ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 48 3 424 - 432 2005年04月 研究論文(学術雑誌) 
    Wild jungle crows (Corvus macrorhynchos) captured from three different areas of Tokyo were examined to evaluate environmental contamination of dioxins. In addition to the pathologic examination of their whole body, accumulation of dioxins, mRNA expression of the aryl hydrocarbon receptor (AhR), and pentoxyresorufin-O-depenthylase (PROD) activity in the liver were determined. Marked histopathologic changes were observed in the thyroid glands, especially in the crows from the urban downtown area. Levels of dioxins and their toxic equivalents (TEQs) and AhR mRNA expression in the livers of the crows from the urban area were higher than those from the suburban area. There was a high correlation between the levels of TEQs and PROD activity. The results of the present study demonstrated that jungle crows possess AhR-mediated toxicologic pathways similar to those of mammals and suggest the possibility that the thyroidal changes observed in the adult crows from the urban areas are one of the toxic manifestations resulting from exposure to dioxins and other environmental chemicals.
  • T Agusa, T Kunito, H Iwata, Monirith, I, TS Tana, A Subramanian, S Tanabe
    ENVIRONMENTAL POLLUTION 134 1 79 - 86 2005年03月 研究論文(学術雑誌) 
    Mercury (Hg) concentrations in human hair and fish samples from Phnom Penh, Kien Svay, Tomnup Rolork and Batrong, Cambodia, collected in November 1999 and December 2000 were determined to understand the status of contamination, and age-and sex-dependent accumulation in humans and to assess the intake of mercury via fish consumption. Mercury concentrations in human hair ranged from 0.54 to 190 mug/g dry wt. About 3% of the samples contained Hg levels exceeding the no observed adverse effects level (NOAEL) of WHO (50 mug/g) and the levels in some hair samples of women also exceeded the NOAEL (10 mug/g) associated with fetus neurotoxicity. A weak but significant positive correlation was observed between age and Hg levels in hair of residents. Mercury concentrations in muscle of marine and freshwater fish from Cambodia ranged from <0.01 to 0.96 mug/g wet wt. Mercury intake rates were estimated on the basis of the Hg content in fish and daily fish consumption. Three samples of marine fish including sharp-tooth snapper and obtuse barracuda, and one sample of sharp-tooth snapper exceeded the guidelines by US EPA and by Joint FAO/WHO Expert Committee on Food Additives (JECFA), respectively, which indicates that some fish specimens examined (9% and 3% for US EPA and JECFA guidelines, respectively) were hazardous for consumption at the ingestion rate of Cambodian people (32.6 g/day). It is suggested that fish is probably the main source of Hg for Cambodian people. However, extremely high Hg concentrations were observed in some individuals and could not be explained by Hg intake from fish consumption, indicating some other contamination sources of Hg in Cambodia. (C) 2004 Elsevier Ltd. All rights reserved.
  • A Sudaryanto, S Takahashi, H Iwata, S Tanabe, M Muchtar, H Razak
    MARINE POLLUTION BULLETIN 50 2 227 - 236 2005年02月 研究論文(学術雑誌)
  • S Niimi, MX Watanabe, EY Kim, H Iwata, G Yasunaga, Y Fujise, S Tanabe
    MARINE POLLUTION BULLETIN 51 8-12 784 - 793 2005年 研究論文(学術雑誌) 
    This study presents full-length cDNA sequences of CYP1A1 and 1A2, in common minke whale (Balaenoptera acutorostrata) from the North Pacific. Both CYP1A1 and CYP1A2 cDNAs had an open reading frame of 516 amino acid residues, and predicted molecular masses were 58.3 kDa and 58.1 kDa, respectively. The deduced full-length amino acid sequence of CYP1A1 revealed higher identities with those of sheep (86%) and pig (87%), and that of CYP1A2 was most closely related to human (82%) and monkey CYP1A2 (82%) among species from which CYP1A2 has been isolated so far. Differences in certain conserved and functional amino acid residues of CYP1A1 and 1A2 between common minke whale and other mammalian species indicate the possibility of their specific metabolic function. Concentrations of organochlorine compounds (OCs) including PCBs and DDTs analyzed in common minke whale liver showed no significant correlation with hepatic mRNA expression levels of CYP1A1 and CYP1A2, indicating no induction of these enzymes by such OCs. (c) 2005 Elsevier Ltd. All rights reserved.
  • Hisato Iwata
    Chūdoku kenkyū : Chūdoku Kenkyūkai jun kikanshi = The Japanese journal of toxicology 18 333 - 347 2005年01月
  • T Agusa, T Kunito, G Yasunaga, H Iwata, A Subramanian, A Ismail, S Tanabe
    MARINE POLLUTION BULLETIN 51 8-12 896 - 911 2005年 研究論文(学術雑誌) 
    Concentrations of trace elements (V, Cr, Mn, Co, Cu, Zn, Ga, Se, Rb, Sr, Mo, Ag, Cd, Sn, Sb, Cs, Ba, Hg, Tl, Pb and Bi) were determined in muscle and liver of 12 species of marine fish collected from coastal areas in Malaysia. Levels of V, Cr, Mn, Co, Cu, Zn, Ga, Sr, Mo, Ag, Cd, Sri, Ba and Pb in liver were higher than those in muscle, whereas Rb and Cs concentrations showed the opposite trend. Positive correlations between concentrations in liver and muscle were observed for all the trace elements except Cu and Sn. Copper, Zn, Se, Ag, Cd, Cs and Hg concentrations in bigeye scads from the east coast of the Peninsular Malaysia were higher than those from the west, whereas V showed the opposite trend. The high concentration of V in the west coast might indicate oil contamination in the Strait of Malacca. To evaluate the health risk to Malaysian population through consumption of fish, intake rates of trace elements were estimated on the basis of the concentrations of trace elements in muscle of fish and daily fish consumption. Some specimens of the marine fish had Hg levels higher than the guideline value by US Environmental Protection Agency (EPA), indicating that consumption of these fish at the present rate may be hazardous to Malaysian people. To our knowledge, this is the first study on multielemental accumulation in marine fish from the Malaysian coast. (c) 2005 Elsevier Ltd. All rights reserved.
  • T Kunisue, M Watanabe, H Iwata, A Subramanian, Monirith, I, TB Minh, R Baburajendran, TS Tana, PH Viet, M Prudente, S Tanabe
    ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 47 3 414 - 426 2004年10月 研究論文(学術雑誌) 
    In this study, concentrations of dioxins and related compounds (DRCs)-such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls-were found in human breast milk from women living near dumping sites of municipal waste and reference sites in India, Cambodia, Vietnam, and the Philippines during 1999 to 2000. DRCs were detected in all human breast milk samples analyzed, demonstrating that residents in these Asian developing countries have been exposed to these contaminants. In India, the concentrations of DRCs in human breast milk from women living near the investigated dumping site were notably higher than those from women living near reference sites and from women in other Asian developing countries. Toxic equivalent quantity (TEQ) levels of DRCs were comparable with or higher than those reported in the general populations of developed countries since 1990. In contrast, levels of these contaminants in human breast milk in women from Cambodia and Vietnam were not significantly different between milk from women living near the dumping and reference sites. These results indicate that significant pollution sources for DRCs are present in Indian dumping sites and that residents there have been exposed to relatively higher levels of these contaminants. TEQ levels in human breast milk from the dumping site in India tended to decrease with an increase in the number of previous deliveries by mothers, whereas no significant relationship was observed in Cambodia, Vietnam, or the Philippines. This suggests that mothers who have been exposed to relatively high levels of DRCs transfer greater amounts of these contaminants to the first infant than later ones through breast-feeding, which in turn implies that the first children of these mothers might be at higher risk from DRCs. When the residue levels of DRCs in bovine milk collected from the Indian dumping site and reference sites were examined, TEQ levels in bovine milk from the dumping suggests that bovine milk is a potential source of DRCs for residents living near the dumping site in India. To our knowledge, this is the first comprehensive study on exposure to DRCs of residents living in proximity to open dumping sites of municipal waste in Asian developing countries.
  • EY Kim, H Iwata, Y Fujise, S Tanabe
    MARINE ENVIRONMENTAL RESEARCH 58 2-5 495 - 498 2004年08月 研究論文(学術雑誌) 
    The contaminant-induced cytochrome P450 (CYP) members in minke whale (Balaenoptera acutorostrata) can be potential biomarkers of the contaminant exposure and toxic effects. In this study, we constructed a cDNA library from the liver of minke whale from the North Pacific, and further screened a total of 6930 clones randomly selected in the library for the isolation of cDNA clones encoding novel members of CYP superfamily. The screening revealed the isolation of six novel CYP cDNA clones that are classified into CYP1A, CYP2C, CYP2E, CYP3A, CYP4, and CYP4A subfamilies. The BLAST homology search using the partial cDNA fragments of four CYP subfamilies (CYP1A, CYP2C, CYP2E and CYP4A) demonstrated that the minke whale CYPs were most closely related to pig CYPs (81-91%). Identification of multiple CYP genes in marine mammal species such as minke whale will provide new insights into the metabolic or toxicological functions of individual CYP members. (C) 2004 Elsevier Ltd. All rights reserved.
  • T Yasui, EY Kim, H Iwata, S Tanabe
    MARINE ENVIRONMENTAL RESEARCH 58 2-5 113 - 118 2004年08月 研究論文(学術雑誌) 
    The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its related planar halogenated aromatic hydrocarbons (PHAHs) are mediated by the aryl hydrocarbon receptor (AHR). To investigate the potential sensitivity to PHAHs and the evolutional diversity of AHR in aquatic birds, AHR cDNAs were initially cloned and sequenced from the livers of a black-footed albatross (Diomedea nigripes) and a common cormorant (Phalacrocorax carho). In this study, we report the identification of two distinct AHR paralog genes in these species. The two full-length AHR cDNAs from albatross were highly divergent (33% overall amino acid identity, and 60% identity in the N-terminal half). Phylogenetic analysis showed that one of them belongs to the AHR1 clade and the other one to the AHR2 clade, which has been identified only from fishes, but not yet from mammals and birds. Albatross AHR1 encoded a 861-residue protein with a predicted molecular mass of 96.7 kDa, and in the case of albatross AHR2, 925 amino acids and 100.7 kDa. From cormorant liver, the full-length AHR1 cDNA and the partial AHR2 cDNA were cloned. This result strongly suggests that bird species also possess two distinct AHR genes (AHR1 and AHR2). To our knowledge, this is the first report on the presence of an AHR2-like isoform in bird species as well as in fish. (C) 2004 Elsevier Ltd. All rights reserved.
  • H Sakai, H Iwata, EY Kim, S Tanabe, N Baba
    MARINE ENVIRONMENTAL RESEARCH 58 2-5 107 - 111 2004年08月 研究論文(学術雑誌) 
    Constitutive androstane receptor (CAR) plays a key role in the transcriptional regulation of CYP2B, 2C and 3A genes in response to phenobarbital, ortho-chlorine substituted polychlorinated biphenyls (PCBs) and sex steroids in rodents and human. However, studies addressing CAR are limited to certain laboratory animals and cell lines, and there is little information on the presence of CAR and its physiological and contaminant-related functions in wildlife. While aquatic mammals including seal species are at the top of food chain and highly contaminated by xenochemicals such as PCBs, induction of CYP2/3 subfamilies by such chemical exposure and their regulatory mechanisms have not yet been established in these animals. To investigate mechanisms of CAR-CYP's signaling pathways in aquatic mammals, we initially attempted to isolate CAR cDNA in the liver of northern fur seals (Callorhinus ursinus) from off-Sanriku, Japan. The full-length CAR cDNA had an open reading frame of 1047 bp that encodes a protein containing 348 amino acids. Comparison of the amino acid sequence of CAR from the fur seal with those from other mammalian species showed high identities with CARs from human (83%), monkey (82%), rat (73%) and mouse (73%), revealing a conservation of CAR among the mammalian species. Phylogenetic analysis demonstrated that the fur seal CAR was classified into CAR clade and not into PXR/BXR or VDR clade, suggesting the CARs would be conserved among, divergent mammals including aquatic species. With our concomitant paper, where CAR cDNA isolation from the liver of Baikal seal is reported (Iwata et al., in preparation), to our knowledge, this is the first study on the identification of CAR cDNA from wildlife species. (C) 2004 Elsevier Ltd. All rights reserved.
  • A Sudaryanto, S Takahashi, H Iwata, S Tanabe, A Ismail
    ENVIRONMENTAL POLLUTION 130 3 347 - 358 2004年08月 研究論文(学術雑誌) 
    Concentration of butyltin compounds (BTs), including tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) and total tin (SigmaSn) were determined in green mussel (Perna viridis), 10 species Of Muscle fish and sediment from coastal waters of Malaysia. BTs were detected in all these samples ranging from 3.6 to 900 ng/g wet wt., 3.6 to 210 ng/g wet wt., and 18 to 1400 ng/g dry wt. for mussels, fish and sediments, respectively. The concentrations of BTs in several locations of this study were comparable with the reported values from some developed countries and highest among Asian developing nations. Considerable concentration of BTs in several locations might have ecotoxicological consequences and may cause concern to human health. The parent compound TBT was found to be highest than those of its degradation compounds, DBT and MBT, suggesting recent input of TBT to the Malaysian marine environment. Significant positive correlation (Spearman rank correlation: r(2) = 0.82, P < 0.0001) was found between BTs and SigmaSn, implying considerable anthropogenic input of butyltin compounds to total tin contamination levels. Enormous boating activities may be a major source of BTs in this country, although aquaculture activities may not be ignored. (C) 2004 Elsevier Ltd. All rights reserved.
  • A Kubota, H Iwata, S Tanabe, K Yoneda, S Tobata
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 38 14 3853 - 3859 2004年07月 研究論文(学術雑誌) 
    Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) were determined in the liver and pectoral muscle of common cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan. To clarify the toxicokinetic behaviors and potential toxicities of these chemicals, the present study addresses life-stage- and tissue-specific accumulation of the congeners. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were in the range of 360 to 50 000 pg/g lipid weight in the liver and 310 to 12 000 pg/g lipid weight in the pectoral muscle. Among congeners, for which toxic equivalency factors were assigned, PCB126, 2,3,4,7,8-P5CDF, and 1,2,33,8-P5CDD made a greater contribution to total TEQs in the liver. Hepatic concentrations of T-4- to H6CON, P-5- and H(6)CDFs, and Co-PCBs (except PCB77) significantly increased with growth of cormorants, leading to life-stage-related compositional changes. The concentration ratios of liver to pectoral muscle revealed preferential accumulation of higher chlorinated congeners in hepatic tissue. For most congeners, concentration ratios significantly increased with an increase in hepatic total TEQs, suggesting their con centration-dependent hepatic sequestration. These results imply the presence of hepatic binding protein(s) such as cytochrome P450, inducible by these chemicals, which may function as a binding species different from aryl hydrocarbon receptor. On the basis of these results, we conclude that the toxicokinetic behavior of each congener is life-stage-, tissue-, and concentration-dependent. TEN in wildlife populations exposed to multiple congeners with varying concentrations should be used with caution for risk assessment, even within a species.
  • H Iwata, M Watanabe, Y Okajima, S Tanabe, M Amano, N Miyazaki, EA Petrov
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 38 13 3505 - 3513 2004年07月 研究論文(学術雑誌) 
    To assess the toxicokinetic behavior and potential toxicity of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) in Baikal seals, congener-specific levels and tissue distribution were evaluated in the liver and blubber, and the effects of biological factors including sex and growth were assessed. Total 2,3,7,8-TCDD toxic equivalents (TEQs) were in the range of 210-920 pgTEQ/g fat wt (180-800 pgTEQ/g wet wt) in the blubber and 2907800 pgTEQ/g fat wt (10-570 pgTEQ/wet wt) in the liver. Non-ortho coplanar PCB126 was the most TEQ-contributed congener accounting for 37-59% of the total THIS in the liver. From the unique congener profiles, weak metabolic properties of Baikal seals for 2,3,7,8-TCDF and 1,2,3,7,8-P-5-CDF are suggested. Concentrations of most congeners linearly increased with age in male seals, whereas in adult females the levels revealed an age-related decline. The increasing and declining rates were congener-specific. Maternal transfer rates of 5 representative congeners from adult female to pup through lactation, which was estimated from male-female differences in the body burden, was 1.1 ngTEQ/kg/day for the first pup and decreased with every lactational epoch. The liver-blubber distribution of 1,2,3,4,7,8-H6CDD, 1,2,3,6,7,8-H6CDD, PCB81, PCB126, and PCB169 was dependent on the hepatic total TEQ, indicating hepatic sequestration by induced cytochrome P450 (CYP). These results indicate that congener profile in Baikal seals is governed by complex factors including sex, tissue concentration, binding to CYP, and rates of absorption and meta bolism/excretion.
  • NH Minh, M Someya, TB Minh, T Kunisue, H Iwata, M Watanabe, S Tanabe, PH Viet, BC Tuyen
    ENVIRONMENTAL POLLUTION 129 3 431 - 441 2004年06月 研究論文(学術雑誌) 
    Despite the ban on persistent organochlorines (OCs) in most of the developed nations, their usage continued until recently in many Asian developing countries including Vietnam, for agricultural purposes and vector-borne disease eradication programs. In this study. we collected human breast milk samples from the two big cities in Vietnam: Hanoi (n = 42) and Hochiminh (n = 44) and determined the concentrations of persistent OCs such as PCBs, DDT and its metabolites (DDTs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB). chlordane compounds (CHLs) and tris-4-chlorophenyl-methane (TCPMe). The contamination pattern of OCs was in the order of DDTs > PCBs > HCHs > CHLsapproximate toHCBapproximate toTCPMe. Compilation of available data indicated that DDT residue levels in human breast milk from Vietnam were among the highest values reported for Asian developing countries as well as developed nations. This result suggests recent usage of DDTs in both north and south Vietnam. Interestingly, in both cities, the p,p'-DDT portion was higher in multiparas than those in primiparas. Considering the fact that the interval between the first and the second child of a mother in Vietnam is usually short, this result probably indicates continuous intake of DDTs in the population. Analysis of infant exposure to DDTs via breast milk suggested that the daily intake rates for number of individuals are close to or above the threshold for adverse effects which may raise concern on children health. (C) 2004 Elsevier Ltd. All rights reserved.
  • Molecular cloning and expression analysis of three metallothionein isoforms in sea turtles.
    Anan, Y, Kim, E.-Y, Kunito, T, Iwata, H, Tanabe, S
    Proceedings of 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances, March 2004, Matsuyama, Japan. 213-217  2004年
  • Contamination by arsenic and other trace elements in drinking water and residents in Vietnam.
    Agusa, T, Kunito, T, Fujihara, J, Kubota, R, Iwata, H, Minh, T.B, Trang, P.T.K, Viet, P.H, Tanabe, S
    Proceedings of 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances, March 2004, Matsuyama, Japan. 48-52  2004年
  • AGUSA T, KUNITO T, FUJIHARA J, KUBOTA R, MINH T B, TRANG P T K, SUBRAMANIAN A, IWATA H, VIET P H
    Biomedical Research on Trace Elements 15 4 339 - 341 2004年
  • N Kajiwara, S Matsuoka, H Iwata, S Tanabe, FCW Rosas, G Fillmann, JW Readman
    ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 46 1 124 - 134 2004年01月 研究論文(学術雑誌) 
    Wide ranges of organochlorine residues were determined in the blubber of franciscana (Pontoporia blainvillei), estuarine dolphin (Sotalia guianensis), Atlantic spotted dolphin (Stenella frontalis), and long-beaked common dolphin (Delphinus capensis) incidentally caught along Brazilian coastal waters. Concentrations of DDTs and PCBs were the highest, followed by CHLs, TCPMOH, dieldrin, TCPMe, heptachlor epoxide, HCB, and HCHs. Unexpectedly, significant pollution of PCBs, DDTs, TCPMe, and TCPMOH were observed in cetaceans from Brazil, implying the occurrence of local sources in the Southern Hemisphere comparable to those in the Northern Hemisphere, probably by high industrialization in Brazil. On the other hand, CHLs, HCB, HCHs, heptachlor epoxide, and dieldrin residue levels in Brazilian dolphins were much lower than those in other species from the Northern Hemisphere. Significant correlations of TCPMe and TCPMOH were found along with PCBs and DDTs, indicating the highly bioaccumulative nature of all these compounds and/or possible similar pollution sources.
  • Monirith, I, T Kunisue, H Iwata, S Tanabe, TS Tana
    MARINE POLLUTION BULLETIN 46 10 1341 - 1348 2003年10月 研究論文(学術雑誌)
  • Hoshino, H, Fujita, S, Goto, Y, Isono, T, Ishinazaka, T, Sakurai, Y, Iwata, H, Kazusaka, A, Ishizuka, M, Tanabe, S
    Japanese Journal of Environmental Toxicology 6 1 1 - 10 2003年 [査読有り]
  • EY Kim, ME Hahn, H Iwata, S Tanabe, N Miyazaki
    MARINE ENVIRONMENTAL RESEARCH 54 3-5 285 - 289 2002年09月 研究論文(学術雑誌) 
    Species differences in sensitivity to related planar halogenated aromatic hydrocarbons (PHAH) add significant uncertainty in assessing the ecological risk to aquatic mammals. To investigate mechanisms of PHAH sensitivity in aquatic mammals, we cloned and sequenced the cDNA of Baikal seal aryl hydrocarbon receptor (AHR), an intracellular protein that initiates PHAH-mediated effects. The Baikal seal AHR cDNA has an open reading frame of 843 amino acid residues with a predicted molecular mass of 94.6 kDa. Comparison of AHR amino acid sequences indicated a high degree of sequence conservation (98%) between Baikal and harbor seals. The high conservation of AHRs between Baikal and harbor seals indicates that these seals express AHR proteins closely related structurally. In our previous report (Kim & Hahn, 2002), the dioxin-binding affinity of the harbor seal AHR was at least as high as that of the AHR from a dioxin-sensitive strain of mice, suggesting that this seal species may be sensitive to PHAH effects. This implies that Baikal seal may also be sensitive to dioxin effects. (C) 2002 Elsevier Science Ltd. All rights reserved.
  • KQ Sakamoto, T Kunisue, M Watanabe, Y Masuda, H Iwata, S Tanabe, F Akahori, M Ishizuka, A Kazusaka, S Fujita
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 21 4 842 - 847 2002年04月 研究論文(学術雑誌) 
    Polychlorinated biphenyls (PCBs), including coplanar congeners, hexachlorocyclohexane isomers, chlordane-related compounds, and hexachlorobenzene, were found in the breast muscle of Steller's sea eagles (SSE) and white-tailed sea eagles (WSE) threatened species, collected in Hokkaido, Japan, during the two years from 1998 to 1999. Both PCBs and DDTs were the most notable compounds, with concentrations one to two orders of magnitude higher than the other compounds, that is, from 120 to 39,000 and from 68 to 15,000 ng/g wet weight, respectively. Non-ortho (International Union of Pure and Applied Chemistry [IUPAC] 77, 126, and 169) and mono-ortho (IUPAC 105, 118, and 156)-substituted coplanar PCB congeners amounted to 9.2 to 740 pg/g of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents derived from the World Health Organization, Paris, France (WHO), toxic equivalent factors. The atmospheric PCBs and DDTs in eastern Siberian cities, such as Khabarovsk and Magadan, have been reported to be much higher than Hokkaido and the North Pacific. Thus, we speculated that the eagles might have been contaminated in these areas, where they spend most of the year except winter, which they spend in eastern Siberia. Adult eagles accumulated more PCBs and DDTs than younger ones. The patterns of PCB congeners were also found to change, depending on the age of the eagle examined; adult eagles showed relatively higher proportions of highly chlorinated PCBs than juvenile eagles did. This difference would be related to the efficiency of the excretion and the metabolism of each PCB congener in the eagles.
  • Chiba, I, A Sakakibara, H Iwata, M Ishizuka, S Tanabe, F Akahori, A Kazusaka, S Fujita
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 21 4 794 - 806 2002年04月 研究論文(学術雑誌) 
    From 16 largha seats (Phoca largha) and 15 ribbon seals (Phoca fasciata) in the coastal waters of Hokkaido, Japan, blubber chlorinated hydrocarbon (CHC) levels and hepatic cytochrome P450 (CYP) catalytic activities and their immunochemically detected protein content levels were measured. Concentrations of DDTs (2,2-bis(4-chlorophenyl)-1,1-dichloroethylene,p,p'-DDE; 2,2-bis(4-chlorophenyl)-1,1-dichloroethane,p,p'-DDD; dichlorodiphenyltrichloroethane, p,p'-DDT), polychlorinated biphenyl congeners (PCBs), and chlordane compounds (oxychlordane, chlordanes, and nonachlors) in both species were in the range of 290 to 5,300, 420 to 4,000, and 130 to 1,500 ng/g lipid weight, respectively. Aryl hydrocarbon receptor (AhR) agonists, non-ortho (IUPAC 77 and 126) and mono-ortho (IUPAC 105, 118, and 156) coplanar PCB congeners, were also detected, and the 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) toxic equivalents (TEQs) were 4.9 to 120 pg TEQ/g lipid weight. Cross-reactive proteins with polyclonal antibodies against rat CYP1A1 and CYP3A2 were notably detected in seal liver microsomes. Interestingly, a polyclonal antibody against rat CYP2B1 recognized proteins only at trace levels. In largha seals, both levels of alkoxyresorufin- (methoxy-, ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase (AROD) activities and proteins detected by polyclonal antibodies against rat CYP1A1 were significantly correlated with the concentrations of individual coplanar PCB congeners, total TEQs, and total PCBs. Threshold concentrations for TEQs in blubber of the largha seal to induce hepatic CYP1A protein and EROD activity were estimated to be 8.5 and 19 pg TEQ/g fat weight, respectively. In ribbon seals, similar correlations were not detected, although the TEQ levels were not significantly lower than those in largha seals. These results suggest that AROD activity and CYP1A1 protein in the liver of the largha seal could be a biomarker for the exposure to AhR agonists such as coplanar PCB congeners. This study also indicates differences in AhR-mediated responses to the CHC exposures between largha and ribbon seals.
  • APX de Brito, S Takahashi, D Ueno, H Iwata, S Tanabe, T Kubodera
    MARINE POLLUTION BULLETIN 45 1-12 348 - 361 2002年 研究論文(学術雑誌) 
    Organochlorine (OCs) and butyltin (BTs) residues were determined in deep-sea organisms collected from the western North Pacific, off-Tolioku, Japan. Among OCs, concentrations of polychlorinated biphenyls (PCBs') and DDTs (DDTs and its metabolites) were the highest in deep-sea organisms (maximum concentrations of 6700 and 13,000 ng/g lipid wt, respectively). Chlordane compounds (CHLs) were the next most abundant OCs. and hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) were the lowest. BTs were also detected at maximum concentrations of 570 ng/g wet wt. Concentrations of PCBs, CHLs and BTs in deep-sea organisms collected front the western North Pacific, off-Tohoku, were generally lower than those in deep-sea and shallow water organisms from Japanese coastal waters. On the other hand, considerable variations in the concentrations of OCs were found among deep-sea organisms analyzed. Several carnivorous fishes such as snubnosed eel. lanternshark and grenadiers accumulated some OCs such as PCBs, DDTs and CHLs at high concentrations of up to a few mug/g levels. In addition, the residue pattern of OCs and BTs in fishes showed a specific trend according to the sampling depth; higher concentrations of PCBs, DDTs and CHLs and lower concentrations of HCHs, HCB and BTs were found in fishes collected from greater depth (similar to1000 m) compared to those from shallower waters. This trend is consistent with the results of our earlier study on mesopelagic myctophid fishes. Results of this study suggest vertical transport of hydrophobic OCs such as PCBs, DDTs and CHLs and its accumulation in benthic deep-sea organisms. (C) 2002 Elsevier Science Ltd. All rights reserved.
  • D Ueno, H Iwata, S Tanabe, K Ikeda, J Koyama, H Yamada
    MARINE POLLUTION BULLETIN 45 1-12 254 - 261 2002年 研究論文(学術雑誌) 
    Concentrations of persistent organochlorines (OCs) such as PCBs, DDTs, chlordanes (CHLs), HCHs and HCB were determined in the liver of bluefin tuna (Thunnus thynnus) collected from Japanese coastal waters in order to elucidate accumulation profiles and to evaluate the suitability of this species as a biomonitor for pollution in the open sea ecosystem. Concentrations of PCBs, DDTs and CHLs in bluefin tuna increased significantly with body length (30-190 cm). HCHs and HCB residues were comparable among all the sampling regions, and the levels of these chemicals did not show correlation with body length. These results suggest significance of dietary uptake of PCBs, DDTs and CHLs compared to the intake via the gill. On the other hand, equilibrium partitioning with ambient water is a major determinant of the levels of HCHs and HCB in tuna. Body-Length Normalized Values (BLNV) of PCBs, DDTs and CHLs concentrations in bluefin tuna were calculated using the linear regression equation obtained from the plot of concentrations and body length. BLNV of these chemicals on a lipid wt basis, which was adjusted for 100 cm body length, were indicative of the present state water pollution by PCBs, DDTs and CHLs. These results suggest that bluefin tuna is a suitable bioindicator for monitoring OCs contamination in the open sea ecosystem. (C) 2002 Elsevier Science Ltd. All rights reserved.
  • Hisato Iwata, Kouichi Yoshinari, Masahiko Negishi, John J Stegeman
    Comparative Biochemistry and Physiology - C Toxicology and Pharmacology 131 4 501 - 510 2002年 研究論文(学術雑誌) 
    The mammalian constitutively active receptor (CAR) is a novel ligand-activated transcription factor that participates in controlling the expression of cytochrome P450 2B (CYP2B) genes in response to pharmaceutical agents (phenobarbital) and halogenated aromatic hydrocarbons (ortho-substituted PCBs). The occurrence and physiological function of this protein are as yet unknown in marine animals, where there has been a paradoxical lack of induction by PB-type chemicals. One approach to understanding CAR function is to study the evolutionary history of processes such as CAR-CYP2B coupling. In this study, CAR function was evaluated in a representative teleost fish (scup, Stenotomus chrysops). Treatment of scup with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is one of the most potent CYP2B inducers in mouse, caused no increase in hepatic alkoxyresorufin O-dealkylase activity nor in immunodetectable CYP2B-like protein levels. Western blot analyses of scup livers using anti-human CAR antisera revealed the occurrence of a putative CAR homologue in nuclear and cytoplasmic fractions, but no nuclear accumulation of CAR following TCPOBOP treatment, which is a first step regulating the transcriptional activation of CYP2B genes in mouse. Immunohistochemical study also showed no translocation of CAR into nucleus in the hepatocytes of TCPOBOP-treated scup. These results suggest that there may be species-specific differences in CAR activation or CAR-CYP2B coupling signaling transduction in fish from those in mouse. © 2002 Elsevier Science Inc. All rights reserved.
  • Y Maruyama, H Teraoka, H Iwata, A Kazusaka, S Fujita
    NEUROCHEMISTRY INTERNATIONAL 38 7 567 - 572 2001年06月 研究論文(学術雑誌) 
    Naturally occurring neurotoxins, 6,7-dihydroxy-1,2,3,3-tetrahydroisoquinolines (DHTIQs), thought to be the causative agents of Parkinsonism. DHTIQs including norsalsolinol have been found in the mammalian central nervous system. Norsalsolinol can be formed by a non-enzymatic Pictet-Spengler condensation reaction between dopamine and formaldehyde, and has been detected in the urine of Parkinsonian patients. However, the effects of DHTIQs on the secretion of dopamine, as well as other neurotransmitters, are not well understood. This study investigated the effects of norsalsolinol on dopamine secretion from nerve growth factor-differentiated PC12 cells. Norsalsolinol (1-100 muM) pretreatment suppressed both ATP (100 muM)- and K(+) (50 mM)-induced dopamine secretion from PC12 cells in a concentration-dependent fashion, but did not affect basal dopamine secretion. In beta -escin-permeabilized PC12 cells, norsalsolinol pretreatment suppressed Ca(2+) (pCa = 4-8)-induced dopamine secretion, but did not inhibit the secretagogue-induced change in intracellular Ca(2+) concentration. These results suggest that norsalsolinol causes the inhibition of secretagogue-induced dopamine secretion from PC12 cells without altering intracellular Ca(2+) concentration. Inhibition of dopamine secretion by norsalsolinol may also be involved in postural abnormality in Parkinson's disease. (C) 2001 Elsevier Science Ltd. All rights reserved.
  • Chiba, I, A Sakakibara, Y Goto, T Isono, Y Yamamoto, H Iwata, S Tanabe, K Shimazaki, F Akahori, A Kazusaka, S Fujita
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 20 5 1092 - 1097 2001年05月 研究論文(学術雑誌) 
    Chlorinated hydrocarbon (CHC) levels in the blubber of larga seals (Phoca largha) and ribbon seals (Phoca fasciata) collected from the coastal waters of Hokkaido, Japan, were determined in order to assess the hormonal effects of CHC exposure in free-ranging pinnipeds. Plasma thyroid hormone levels, including total thyroxine (T4), free thyroxine (free T4), total triiodothyronine (T3), and free triiodothyronine (free T3), were also measured. Higher concentrations of polychlorinated biphenyl congeners (PCBs), dichlorodiphenyltrichloroethane and its metabolites, and chlordane compounds were found in the range of 380 to 2,600 ng/g, 350 to 2,600 ng/g, and 120 to 760 ng/g on a wet-weight basis, respectively. Spearman rank correlation analyses showed that in larga seals, plasma total T3 and free T3 levels negatively correlated with levels of all the CHCs analyzed, although there was no such correlation between total or free T4 levels and CHC concentrations. In ribbon seals, total T3 levels significantly decreased with an increase of di-ortho PCB (PCB 170 and 180) residues. These findings indicated that the plasma T3 deficiency could be associated with some CHC exposure in larga and ribbon seals and that the responses of plasma thyroid hormones may be useful biomarkers for CHC exposure in ribbon seals.
  • Shoichi Fujita, Issei Chiba, Mayumi Ishizuka, Hidenobu Hoshi, Hisato Iwata, Akihito Sakakibara, Shinsuke Tanabe, Akio Kazusaka, Makihiko Masuda, Yasushi Masuda, Hajime Nakagawa
    Biomarkers 6 1 19 - 25 2001年 研究論文(学術雑誌) 
    The impact of environmental pollution on selected animals was tested by monitoring the hepatic content of cytochromes P450 and their enzyme activities or by calculating TEQ values from the concentration of pollutants in the body. Fish-eating Stellars Sea Eagles, Haliaeetus pelagicus, found dead in the northern part of Hokkaido island accumulated high levels of PCBs and DDT and metabolites. The TEQ values calculated from the PCB concentration in the eagles were high enough to cause a significant toxic effect in other birds living in the same environment. Some of these birds were also contaminated with high concentrations of lead. Spotted seals, Phoca largha, captured along the coast-line of Hokkaido accumulated PCBs in their fat at about 100 million times the concentrations in the surface sea water. The levels of expressions of hepatic microsomal CYP 1A1 and related enzyme activities in these seals showed good correlation to the levels of PCBs accumulated in the fat. The fresh water crabs, Eriocheir japonicus, were captured from three different rivers with various degrees of pollution. The P450 content and the related enzyme activities showed good correlation to TEQ values obtained from the concentrations of PCBs and PCDDs in the crabs from the rivers. The wild rodents, Clethrionomys rufocanus, were captured from urban, agricultural, and forest areas in Hokkaido. Those from the forest area had the lowest CYP content and related enzyme activities, comparable to those in laboratory-raised animals. Those from the urban areas, presumably contaminated with PAHs from fuel combustion, showed increased CYP 1A1 content and related enzyme activities. Those from the agricultural areas showed increased levels of CYP 1A1, 2B, 2E1. Rats treated with some of the agrochemicals used in the area resulted in a similar pattern of induction. It is concluded that P450 can be a useful biomarker for assessing the environmental impact of chemical pollutants on wild animals.
  • I. Chiba, A. Sakakibara, Y. Goto, T. Isono, Y. Yamamoto, H. Iwata, S. Tanabe, K. Shimazaki, F. Akahori, A. Kazusaka, S. Fujita
    Environmental Toxicology and Chemistry 20 5 1092 - 1097 2001年 研究論文(学術雑誌) 
    Chlorinated hydrocarbon (CHC) levels in the blubber of larga seals (Phoca largha) and ribbon seals (Phocafasciata) collected from the coastal waters of Hokkaido, Japan, were determined in order to assess the hormonal effects of CHC exposure in free-ranging pinnipeds. Plasma thyroid hormone levels, including total thyroxine (T4), free thyroxine (free T4), total triiodothyronine (T3), and free triiodothyronine (free T3), were also measured. Higher concentrations of polychlorinated biphenyl congeners (PCBs), dichlorodiphenyltrichloroethane and its metabolites, and chlordane compounds were found in the range of 380 to 2, 600 ng/g, 350 to 2, 600 ng/g, and 120 to 760 ng/g on a wet-weight basis, respectively. Spearman rank correlation analyses showed that in larga seals, plasma total T3 and free T3 levels negatively correlated with levels of all the CHCs analyzed, although there was no such correlation between total or free T4 levels and CHC concentrations. In ribbon seals, total T3 levels significantly decreased with an increase of di-ortho PCB (PCB170.and 180) residues. These findings indicated that the plasma T3 deficiency could be associated with some CHC exposure in larga and ribbon seals and that the responses of plasma thyroid hormones may be useful biomarkers for CHC exposure in ribbon seals.
  • H Iwata, JJ Stegeman
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 271 1 130 - 137 2000年04月 研究論文(学術雑誌) 
    Knowledge about the expression sites of cytochrome P450 1A (CYP1A) mRNA is crucial for a better understanding of the physiological function of CYP1A. We investigated the cellular localization of CYP1A mRNA in chemically untreated fish by use of an in situ reverse transcription-polymerase chain reaction (IS RT-PCR technique. The fathead minnow (Pimephales promelas) was formalin-fixed, and paraffin-embedded. Sections (5 mu m) were treated with trypsinogen. Following reverse transcription of CYP1A mRNA, the cDNA was amplified in situ by PCR with specific primers. Detection of the amplicons was accomplished by a second PCR performed with digoxigenin-labeled dUTP. CYP1A mRNA expression was detected in cytoplasm of chondroid cells surrounding hyaline cartilage in gill arches. This result was consistent with that of immunohistochemical analysis with a CYP1A1-specific monoclonal antibody. CYP1A mRNA also was found in stratified squamous epithelium of the pharynx and gill arches, but no staining was detected in those cells by immunohistochemical analysis. The results indicate that IS RT-PCR is an effective/sensitive technique for localizing low level CYP1A expression. In addition, the sites where we identified expression of CYP1A are targets of retinoic acid, sonic hedgehog and Hox genes, suggesting that functional CYP1A in vertebrates could participate in craniofacial skeletal development through involvement in the retinoic acid signaling cascade. (C) 2000 Academic Press.
  • 安永 玄太, 田辺 信介, 金 恩英, 岩田 久人, 須藤 明子, 増田 泰, 藤田 正一, 神 和夫
    環境科学会誌 13 1 51 - 59 社団法人 環境科学会 2000年 
    北海道産オオワシ(Haliaeetus pelagicus),オジロワシ(H. albicilla)および岩手県産イヌワシ(Aquila chrysaetos)の肝臓,腎臓および筋肉中微量元素18種を測定した。その結果,V,Ag,CsおよびRbなどの濃度は,他の鳥類と比較して高い値が認められた。しかし,肝臓中のHgおよびCd濃度は相対的に低値を示した。Pb中毒の症状がみられた個体および筋胃内に鉛弾の痕跡が認められた個体は,高いPb濃度を示した。また,銃弾の主成分であるPbと共存含有成分Sbの肝臓中濃度には,正の相関関係が見られ,猛禽類の高濃度Pb蓄積は,主として銃弾由来であることが示唆された。肝臓中のSb濃度の測定は,銃弾由来のPb汚染を判定する手がかりとして活用できよう。
  • H Iwata, M Watanabe, FY Kim, R Gotoh, G Yasunaga, S Tanabe, Y Masuda, S Fujita
    FIRST SYMPOSIUM ON STELLER'S AND WHITE-TAILED SEA EAGLES IN EAST ASIA 91 - 106 2000年 研究論文(国際会議プロシーディングス) 
    Chronic exposure to man-made chemicals, particularly chlorinated hydrocarbons, in raptors has been associated with reproductive impairment and population declines. In addition, incidents of sub-lethal and lethal lead poisoning in raptors through ingestion of spent gunshot have been reported. However, little information is available on the contaminant levels of Steller's Sea Eagle (SSE: Haliaeetus pelagicus) and White-tailed Sea Eagle (WSE: H. albicilla) from Hokkaido, Japan. The objective of this study was to determine the levels of toxic contaminants including polychlorinated biphenyls (PCBs), organochlorine pesticides, and lead in sea eagles wintering in Hokkaido, and to evaluate the ecotoxicological risk based on their concentrations. SSEs and WSEs which were found dead or debilitated and subsequently died in Hokkaido from 1986 to 1998 were analysed. All eagles contained detectable amounts of PCBs, DDTs, hexachlorocyclohexane isomers, chlordane related compounds, and hexachlorobenzene. The highest concentrations of PCBs and DDTs in breast muscles were 18,000 and 17,000 ng/g (wet weight), respectively. Furthermore, non-ortho and mono-ortho substituted coplanar PCB congeners were also detected, leading to 60-540 pg/g of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents derived from WHO toxic equivalence factors in the breast muscles. Our previous survey of contaminants in the Far East showed that atmospheric concentrations of PCBs and DDTs in Khabarovsk and Magadan were much higher than those in Hokkaido and North Pacific, suggesting the potential that some east Siberian cities might be a source of contamination found in eagles. Residue levels of PCBs and DDTs in breast muscles of SSEs were comparable to those of raptors collected after the 1980s from North America. Risk assessments based on the residue levels of coplanar PCB congeners and p,p'-DDE detected in these eagles indicated their potential of hepatic cytochrome P450 1A induction and eggshell thinning. High lead concentrations of over 10,000 ng/g (dry weight) were detected in the livers of some SSEs and WSEs. Three of six dead or moribund SSEs (50%) and three of three WSEs (100%) with livers analyzed for lead died from lead poisoning. Five of the six lead poisoned eagles had lead bullet fragments in their gizzards. The hair of deer was found along with a lead fragment in the intestine of a SSE. In Hokkaido, whole and partial carcasses of deer shot by hunters are left in the field. These are potential sources of lead fragments that are ingested by scavenging raptors during and after the hunting season. Therefore, secondary poisoning by the lead fragment embedded in the tissue of deer is implicated as the main cause of death. Mercury and cadmium concentrations in the tissue of these species were low, implying that the toxicities of these elements were negligible.
  • 安永 玄太, 田辺 信介, 金 恩英, 岩田 久人, 須藤 明子, 増田 泰, 藤田 正一, 神 和夫
    環境科学会誌 13 1 51 - 59 2000年
  • Ikuko Teramitsu, Yukio Yamamoto, Issei Chiba, Hisato Iwata, Shinsuke Tanabe, Yoshihiro Fujise, Akio Kazusaka, Fumiaki Akahori, Shoichi Fujita
    Aquatic Toxicology 51 2 145 - 153 2000年 研究論文(学術雑誌) 
    Marine mammals, being endangered by the chronic exposure of hydrophobic environmental contaminants as an assorting result of global pollution, are especially focused as indicators for organochlorine pollution. The use of contaminant-induced xenobiotic metabolizers, particularly P450 (CYP) 1A, in marine mammals can be effective as potential biomarkers of the contaminant exposure and/or toxic effects. In this study, we identified the first marine mammalian CYPs. Six novel CYP1A cDNA fragments were cloned from the livers of marine mammal species, minke whale (Balaenoptera acutorostrata), dall's porpoise (Phocoenoides dalli), steller sea lion (Eumetopias jubatus), largha seal (Phoca largha), and ribbon seal (Phoca fasciata) by the method of reverse transcription/polymerase chain reaction (RT/PCR) two distinct fragments were from steller sea lion and one fragment each was obtained from the other species. Five of the fragments, one from each species, were classified in the subfamily of CYP1A1, and the other fragment cloned from steller sea lion was designated CYP1A2. Degenerate PCR primers were used to amplify the fragments from liver cDNAs. The deduced amino acid sequences of these fragment CYP1As showed identities ranging from 50.0 to 94.3% with other known vertebrate CYPs in the subfamily of CYP1A, including those from fish, chicken, and terrestrial mammals. The isolated fragments were used to construct a molecular phylogeny, along with other vertebrate CYP1A cDNAs cut down in size to the corresponding region of 265 bp in which those newly determined fragments were cloned. This phylogenetic analysis by the maximum parsimony method using the PHYLIP program suggests two distinct evolutional pathways for aquatic mammalian CYP1As, compatible to a conservative taxonomy. Pinniped genes are clustered together with dog gene, forming a carnivore group, and cetaceans form another branch. Identification of CYP1A genes in marine mammals will be an introductory step to provide new insights into the metabolic or toxicological functions of CYP1As in these animals. (C) 2000 Elsevier Science B.V.
  • J. Falandysz, B. Brudnowska, H. Iwata, S. Tanabe
    Roczniki Państwowego Zakładu Higieny 50 123 - 130 1999年11月 
    The composition and loads of organochlorine pesticides (DDTs, HCBs, HCHs, CHLs) and polychlorinated biphenyls (PCBs) transported with the Vistula River waters to the Gulf of Gdansk in 1991-1992 has been determined. The method of organochlorine compounds measurement was capillary gas chromatography with ECD after adsorption of the analyte on Ambertlite XAD-2, resin and subsequent elution, clean-up and HPLC fraction of the extract. The concentrations of DDTs, HCBs, HCHs, CHLs and PCBs in the Vistula River water ranged between 120-840, 7.6-52, 1600-410,000, 8.1-57 and 120-300 pg/l, respectively. During 12 months period of the study the total load of DDTs, HCBz, HCHs, CHLs and PCBs transported with the Vistula River water to the Gulf of Gdańsk was assessed on 10.54, 0.73, 1377, 0.38 and 5.02 kg, respectively.
  • J. Falandysz, B. Brudnowska, H. Iwata, S. Tanabe
    Roczniki Państwowego Zakładu Higieny 50 39 - 47 1999年10月 
    The concentrations of organochlorine pesticides such as DDTs, HCHs, CHLs, HCB and polychlorinated biphenyls (PCBs) were determined in ambient are samples collected in city of Gdańsk in 1991-1992 to understand concentrations, sources and seasonal distribution. Polyurethane foam plugs were used as adsorbents for collection of persitent organochlorines in ambient air samples. Identification and quantification of organochlorines were carried out using a capillary column gas chromatography and ECD (63Ni) detection. HCB, alpha-HCH, gamma-HCH, p,p'-DDT, o,p'-DDT, p,p'-DDE, o,p'-DDE, p,p'-DDD, o,p'-DDD and PCBs were detected in all samples, while the constituents of technical chlordan were absent in concentration above the detection limit of the method (trans-chlordane < 14 pg/m3, cis-chlordane < 8.1 pg/m3 and trans-nonachlor < 7.4 pg/m3). The concentrations of HCB and PCBs were depended on the air temperatures, hence their main source can be related to a process of degasing from the soil.
  • EBM Khlood, H Miyoshi, H Iwata, A Kazusaka, Y Kon, AH Abou Hadid, EK Moustafe, MH Ghonim, S Fujita
    JAPANESE JOURNAL OF VETERINARY RESEARCH 47 1-2 13 - 23 1999年08月 研究論文(学術雑誌) 
    To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Darns were killed on the 20th. day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects : the fetal resorption amounted to similar to 60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were: absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.
  • EY Kim, R Goto, H Iwata, Y Masuda, S Tanabe, S Fujita
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 18 3 448 - 451 1999年03月 研究論文(学術雑誌) 
    Concentrations of lead, mercury, and cadmium in the liver, kidney, and muscle of four Steller's sea eagles (Haliaeetus pelagicus) and one white-tailed sea eagle (Haliaeetus albicilla) that were found dead or debilitated and subsequently died in Hokkaido, Japan, from 1986 to 1997 were determined. High lead concentrations (>70 mu g/g dry weight) were detected in the liver of two Steller's sea eagles and the white-tailed sea eagle. Lead shot was also found in the intestine and gizzard of one Steller's sea eagle and the white-tailed sea eagle, respectively. Mercury and cadmium concentrations in the tissues of these raptors were low, implying that the toxicities of these elements were negligible. These results indicate that eagles in Hokkaido are suffering from secondary poisoning through ingestion of lead shot embedded in the tissue of their prey.
  • El Bohi M. Khlood, Hiroyuki Miyoshi, Hisato Iwata, Akio Kazusaka, Yasuhiro Kon, ALi H. Abou Hadid, El Kelish Moustafe, Mervat H. Ghonim, Shoichi Fujita
    Japanese Journal of Veterinary Research 46 1-2 13 - 23 1999年02月 
    To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Dams were killed on the 20th day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects: the fetal resorption amounted to∼60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.
  • Organochiorine pesticides and polychlorinated biphenyls in the Vistula river water.
    Rocz.Panstw.Zakl.Hig., 50 2 123 - 30 1999年
  • Orgabichlorine pesticides and polychlorinated biphenyls in ambient air in the city of Gdansk.
    Rocz.Panstw.Zakl.Hig., 50 1 39 - 47 1999年
  • J. Takahashi, Y. Furuhata, A. Ikeda, M. Takahashi, H. Iwata, A. Kazusaka, S. Fujita
    Xenobiotica 29 12 1203 - 1212 1999年 研究論文(学術雑誌) 
    1. The present authors have previously developed a transgenic rat carrying a chimeric gene of the mouse whey acidic protein promoter and the structural portion of human growth hormone (GH) gene. Among this (hGH-TG) rat, a line (low GH rat) missing a male-specific pulsatile GH secretary pattern due to suppression of endogenous GH secretion and having a continuous low GH (hGH and rat GH) level in the peripheral circulation was identified. The latter rat was also characterized as having severe obesity with age. This strain (low Gh rat) was used to correlate the sex-specific secretory pattern of GH with the sex-specific expression of cytochrome P450 (CYP) in rat. 2. Comparisons were made between the low GH rat and the non-transgenic rat as to the expression of liver microsomal CYP isozymes. The following enzyme activities were assessed: testosterone (T) hydroxylation and oxidation ethoxyresorufin O-dealkylation (EROD) bunitrolol (BTL) 4-hydroxylation and T5 α-reduction. Protein expression of CYP1A, CYP2C11, CYP2D, CYP2E1, CYP3A2 and CYP4A1 were also assessed by Western blot analysis. 3. Enzyme activities and protein expression of CYP2C11 (T16 α and 2α-hydroxylase and 17-oxidase activities) and CYP3A2 (T6β and 2β-hydroxylase activities) levels, which are known to be higher in the male than in the female rat, were significantly lower in the adult male low GM rat than in the control male rat. In contrast, CYP2A1 (T7 α-hydroxylase) and T5-α-reductase activities, which are known to be specifically elevated in the female, were significantly higher in the adult male low GH rat than in the control male rat. Thus, the loss of male-specific secretory pattern of GH results in feminization of the pattern of expression of CYP and T5 α-reductase activity in the liver. 4. In contrast to other GH-deficient models so far studied, an increase in CYP4A1 and a decrease in CYP2E1 protein expression were observed in the low GH rat. These trends are consistent with the characteristic phenotype of obesity in the transgenic rat because CYP4A1 and CYP2E1 enhance fatty acid excretion and glyconeogenesis from fatty acids respectively.
  • H Iwata, S Tanabe, T Iida, N Baba, JP Ludwig, R Tatsukawa
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 32 15 2244 - 2249 1998年08月 研究論文(学術雑誌) 
    Tissues of northern fur seals (Callorhinus ursinus) from the Pacific coast of Japan and double-crested cormorants (Phalacrocorax auritus) from the Great Lakes were analyzed in order to explore the enantioselective accumulation of alpha-hexachlorocyclohexane (HCH). The effects of biological and ecological factors such as species, tissue, sex, age, feeding habit, and habitat, which may be attributable to the differences in accumulation between enantiomers, were also investigated. The enantiomeric ratios (ERs) of (+)-/(-)-alpha-HCH in fat tissue of female fur seals, composed of different age groups, collected in 1986 (1.58 +/- 0.25) exhibited greater values than those in abiotic and lower trophic levels previously reported. No age trend of ERs was found in female northern fur seals. There appeared to be a temporal transition of ERs in adult female northern fur seals collected in 1971-1988. Regression analysis showed a significant relationship between ERs and feeding habits (p = 0.003). Analysis of breast muscle of double-crested cormorants exhibited no sex difference in ERs. ERs (1.26 +/- 0.13) in cormorants from Lake Michigan were significantly higher than those (1.01 +/- 0.18) from Lake Superior (p = 0.002), suggesting the effects of factors such as feeding habit and habitat. Enantiomeric accumulation in the body of double-crested cormorants was tissue-specific. No age trend of ERs was seen in breast muscle of cormorants. The result implies that sexual maturity, aging and breeding activities are less effective for changing ERs. The ERs in higher trophic animals could be influenced by species-specific metabolism and transport process in the body as biological factors and by feeding habit and habitat as ecological factors.
  • S Tanabe, M Prudente, H Iwata, N Miyazaki
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 32 15 2355 - 2355 1998年08月
  • M Ishizuka, T Sakiyama, H Iwata, M Fukushima, A Kazusaka, S Fujita
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 17 8 1490 - 1498 1998年08月 研究論文(学術雑誌) 
    The hepatopancreases of freshwater crabs (Eriocheir japonicus) collected from three Japanese rivers (Barato, Shiribetsu, and Tone) were analyzed for planar halogenated aromatic hydrocarbons (HAHs), including polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs). The hepatic glutathione S-transferase (GST)dependent enzyme activities in the crab hepatopancreas were also measured to examine their potential as biomarkers for the contaminants. Crabs from the Tone River, which runs through industrial, agricultural, and urban areas, have the highest concentrations of HAHs (4,100 pg/g fat weight), followed by those from the Barato River (2,430-2,970 pg/g fat weight), whereas crabs from the Shiribetsu River were relatively less contaminated (1,350-1,800 pg/g fat weight). Identification of numerous PCDD and PCDF congeners in crabs from all three rivers provided evidence that one of the major sources of PCDDs and PCDFs was waste incineration. In addition, crabs from the Barato and Shiribetsu Rivers were notably contaminated with 1,3,6,8- and 1,3,7,9-TeCDD congeners, which suggests that a possible source was chlornitrofen, which has been extensively used in paddy fields as a herbicide. Calculation of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin toxic equivalents (TEQs) showed that the causal contaminants of higher TEQs in crabs from the Tone River (94.7 TEQ picograms per gram fat weight) were PCDDs and PCDFs, although the most important contributor to the total TEQs was coplanar PCBs (49.95%). The crab hepatopancreas appeared to have abilities to transfer glutathione to 1-chloro-2,4-nitrobenzene (CDNB) and 3,4-dichloronitrobenzene (DCNB). The crabs with the highest TEQ levels showed the highest GST activities. The current results and our previous data lead us to conclude that cytochrome P450 and GST-dependent enzyme activities (benzo[a]pyrene hydroxylation and CDNB and DCNB conjugation) in freshwater crab hepatopancreases are likely to be useful biomarkers for the contamination of planar aromatic hydrocarbons such as benzo[a]pyrene, PCDDs, PCDFs, and coplanar PCBs.
  • H Hoshi, N Minamoto, H Iwata, K Shiraki, R Tatsukawa, S Tanabe, S Fujita, K Hirai, T Kinjo
    CHEMOSPHERE 36 15 3211 - 3221 1998年06月 研究論文(学術雑誌) 
    In order to understand the residue levels of organochlorine compounds (OCs) and their accumulation patterns in wildlife inhabiting Chubu region, Japan, the concentrations of polychlorinated biphenyls (PCBs), hexachlorocyclohexane isomers (HCHs), DDT compounds (DDTs) and hexachlorobenzene (HCB) were measured in 8 species of terrestrial mammals and 10 species of birds. In view of feeding habits, the contamination levels of OCs were found to be higher in omnivorous mammals than in herbivorous ones, and in fish-eating ones and raptores than in omnivorous birds. In fox and dog, PCB 180 (2, 2', 3, 4, 4', 5, 5'-heptachlorobiphenyl) was the most dominant PCB congener, while in the other species PCB-153 (2, 2', 3, 4', 5, 5'-hexachlorobiphenyl) was the most persistent. The ratios of lower chlorinated PCB congeners (tri- to tetra-) to total PCBs were larger in fish-eating birds than in the other birds. The results indicate that the compositions of PCB congeners would reflect the differences of feeding habits and xenobiotic metabolizing systems among each species. (C) 1998 Elsevier Science Ltd. All rights reserved.
  • S Tanabe, M Prudente, T Mizuno, J Hasegawa, H Iwata, N Miyazaki
    ENVIRONMENTAL SCIENCE & TECHNOLOGY 32 2 193 - 198 1998年01月 研究論文(学術雑誌) 
    Hepatic butyltin concentrations were determined in 63 cetaceans belonging to 14 species and four pinnipeds belonging to two species collected from North Pacific and Asian coastal waters. Butyltin compounds (BTs) including tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MET) were detected in almost all the liver samples suggestive of its worldwide distribution. The elevated residues detected in coastal species and low concentrations found in off-shore species indicate a high degree of butyltin contamination in coastal waters than in the open sea. Mammals inhabiting waters of developed nations were found to contain higher BT concentrations compared with those collected from the waters proximal to developing countries. These observations strongly suggest serious BT contamination in the waters of developed countries than in developing nations at present. Among the samples collected off Japanese coastal waters, lower BT concentrations were found in pinnipeds compared with the cetaceans, suggestive of a possible difference in degradation capacities and excretory moulting between these two groups of animals. The estimated concentration ratio of BT in the liver of killer whale fetus to its pregnant mother was relatively low (0.015), indicative that transplacental transfer of BTs from the mother to her fetus is a deal less. Among the BT breakdown products, DBT was predominant in most of the liver samples analyzed, followed by TBT and MBT.
  • T Tasaki, A Nakamura, S Itoh, K Ohashi, Y Yamamoto, M Masuda, H Iwata, A Kazusaka, T Kamataki, S Fujita
    JOURNAL OF BIOCHEMISTRY 123 1 162 - 168 1998年01月 研究論文(学術雑誌) 
    Dog CYP2D15 was expressed in Sf9 cells with a recombinant baculovirus. Infection of Sf9 insect cells with a recombinant dog CYP2D15-virus resulted in the expression of a protein which cross-reacted with a polyclonal antibody against a dog CYP2D15-specific peptide, The difference spectrum of CO-complex of reduced P450 of the infected cell microsomes had a maximal absorbance at 449 nm, The specific content of P450 was calculated to be 0.56 nmol/mg of Sf9 cell microsomal protein, Although the expressed dog CYP2D15 showed high catalytic activity for the hydroxylations of bunitrolol and imipramine at low substrate concentration (10 mu M), the catalytic activity for that of debrisoquine (50 mu M) was extremely low as compared with that of CYP2D from other species, Dog liver microsomes also showed bunitrolol and imipramine hydroxylase activities, but not debrisoquine hydroxylase activity at the same substrate concentrations, In addition, the expressed CYP2D showed high catalytic activity for imipramine N-demethylation, Thus, our study reveals that the expressed dog CYP2D15 engages in high catalytic activity and has a unique substrate specificity from other CYP2D subfamilies, Western blot analysis suggested that the dog CYP2D15 contents were less than 4% of the total liver P450 content, assuming that 100% of expressed CYP2D15 incorporated heme.
  • Mayumi Ishizuka, Hisato Iwata, Akio Kazusaka, Shigehisa Hatakeyama, Shoichi Fujita
    Xenobiotica 28 11 1029 - 1039 1998年 研究論文(学術雑誌) 
    1. The herbicides butachlor (2-chloro-2',6',diethyl-N-[buthoxymethyl acetanilide) and pretilachlor (2-chloro-2',6'-diethyl-N-[2-propoxyethyl] acetanilide) are widely used in Asia, South America, Europe and Africa. Isoprothioiane (diisopropyl-1,3-dithiolan-2-ylidenemalonate) is used as a fungicide and an insecticide in rice paddies. We administered these agrochemicals to the male rat and examined their effects on cytochrome P450 (P450), glutathione S-transferase (GST), UDP-glucuronosyltransferase (UDPGT), and NAD(P)H-quinone oxidoreductase 1 (NQO1)-related metabolism in the liver. 2. Administration of isoprothiolane, butachlor or pretilachlor to rat induced hepatic P4502B subfamily-dependent enzyme activities (pentoxyresorufin O-depentylation and testosterone 16 β-hydroxylation) up to 271-413% of control, which coincided with the increase in expression levels of the P4502B apoprotein. 3. Activities of GST toward 1-chloro-2,4-nitrobenzene and 3,4-dichloronitrobenzene were slightly induced (127-133% of control) in the liver of the rat treated with these pesticides. On the other hand, marked elevations of UDPGT activities toward p-nitrophenol (164-281% of control) were observed. NQO1-related metabolism (menadione reductase activity) was also induced (123-176% of control) in the liver of rat treated with these agrochemicals. 4. These results indicate that some of the agrochemicals currently in use are capable of inducing phase I and II xenobiotic-metabolizing enzyme activities in an isozyme selective manner. The induction of these activities may disrupt normal physiologic functions related to these enzymes in exposed animals.
  • Yukio Yamamoto, Takafumi Tasaki, Akio Nakamura, Hisato Iwata, Akio Kazusaka, Frank J. Gonzalez, Shoichi Fujita
    Pharmacogenetics 8 1 73 - 82 1998年 研究論文(学術雑誌) 
    The Dark Agouti rat has been proposed as a model for the human debrisoquine 4-hydroxylase polymorphism. Earlier studies suggested that the poor metabolizer phenotype in the Dark Agouti rat is caused by the absence of the expression of CYP2D1 mRNA. Although CYP2D1 is the major enzyme catalyzing debrisoquine 4-hydroxylation, other reports have indicated the involvement of a CYP2D purified from rat hepatic microsomes and presumed to be CYP2D2, which also exhibits this activity. The levels of CYP2D1 and CYP2D2 mRNAs were markedly lower in Dark Agouti as compared to Sprague Dawley rats. Using a baculovirus expression system, recombinant CYP2D1 and CYP2D2 from Spodoptera frugiperda insect cells were examined and were found to both forms catalize debrisoquine 4-hydroxylase activity. These results suggest that reduced debrisoquine 4-hydroxylase activity in the Dark Agouti rat is caused by the low level expression not only of CYP2D1, but also of CYP2D2. Interestingly, bunitrolol 4-hydroxylation was catalyzed by recombinant CYP2D2, while CYP2D1 was inactive toward this substrate. Thus, the low bunitrolol 4-hydroxylation in Dark Agouti rats was caused by the low level of CYP2D2 expression in this rat strain.
  • Takafumi Tasaki, Hisato Iwata, Akio Kazusaka, Shoichi Fujita
    Journal of Biochemistry 123 4 747 - 751 1998年 研究論文(学術雑誌) 
    We have studied the regio- and stereoselectivity of ring-hydroxylation and N-desisopropylation of S(-)- and R(+)-propranolol, using dog liver microsomes and the expressed dog CYP2D15 in insect cells. In dog liver microsomes, 4-hydroxylation was the preferred pathway in S(-)-propranolol oxidation, while N-desisopropylation was the preferred pathway in R(+)-propranolol oxidation. S(-)-Propranolol was preferred over R(+)-propranolol as substrate for 4- and 5-hydroxylations, while R(+)-propranolol was the preferred substrate for N-desisopropylation at higher substrate concentrations. The expressed CYP2D15 had high catalytic activities toward 4-, 5-hydroxylation, as well as N-desisoprspylation of both enantiomers. At the substrate concentrations used, 4-hydroxylation was the preferred pathway for the metabolism of both enantiomers, and S(-)-propranolol was the preferred substrate over R(+)-propranolol for all three monooxygenations catalyzed by CYP2D15. Anti-CYP2D15 peptide antibody strongly inhibited 4- and 5-hydroxylation of both enantiomers in dog liver microsomes, while it did not inhibit their N-desisopropylation. These findings suggest that CYP2D15 is highly responsible for the stereoselective 4- and 5-hydroxylations of propranolol in dog liver microsomes.
  • M Ishizuka, S Yoshino, Y Yamamoto, H Yamamoto, S Imaoka, Y Funae, M Masuda, H Iwata, A Kazusaka, S Fujita
    XENOBIOTICA 27 9 923 - 931 1997年09月 研究論文(学術雑誌) 
    1. During liver regeneration in the male rat, the metabolic activities of imipramine were differentially affected depending on the specific metabolic pathways. Imipramine N-demethylation was markedly reduced whereas 2-hydroxylation showed only a moderate reduction following partial hepatectomy. 2. A slight decline was observed in the hepatic microsomal content of CYP2D apoprotein, whereas a substantial decrease occurred in CYP2C11 content during liver regeneration. Since imipramine 2-hydroxylation and N-demethylation are mediated by CYP2D and 2C11 respectively, metabolic pathway-specific alterations in the activities of imipramine metabolism are explained by the isozyme selective alteration in the levels of CYPs in regenerating liver. 3. No significant effect of regeneration was observed on expression of CYP2B1 and 2E1 apoproteins. CYP3A2 apoprotein, one of the male-specific CYP isoforms, was significantly suppressed in regenerating liner showing a similar pattern of alteration to the levels of CYP2C11. The alteration pattern of the CYP1A1 level was different to the above with a moderate decline at the first day post-operation and a marked rebound thereafter. 4. In the partially hepatectomized male rat, no significant increase in androstenedione 5-alpha reductase activity, an activity predominant in the female rat, was detected. It is concluded that the pattern of alterations of hepatic oxidative metabolism during liver regeneration was not related to the functional feminization of the liver.
  • KS Guruge, H Iwata, H Tanaka, S Tanabe
    MARINE ENVIRONMENTAL RESEARCH 44 2 191 - 199 1997年08月 研究論文(学術雑誌) 
    Concentrations of butyltin compounds were determined in the kidney and liver of various seabirds collected from Japan, Korea, the North Pacific Ocean and the southern Indian Ocean. These compounds were detected in most of the samples, which indicated widespread contamination in higher trophic aquatic animals even in remote areas. The highest mean residue concentrations of butyltins in the kidney (300 ng/g wet wt) and liver (280 ng/g wet wt) were in common cormorants from Lake Biwa, Japan. Laysan albatross from the North Pacific Ocean accumulated higher butyltin residues in the liver (43 ng/g wet wt) among open-ocean birds. Even though the number of samples analysed was small, it can be suggested that birds inhabiting inland to coastal areas had higher exposure to butyltins than those in the ocean. To our knowledge, this is the first study reporting on butyltin pollution in seabirds in global terms. (C) 1997 Elsevier Science Ltd.
  • Hisato Iwata, Shinsuke Tanabe, Takahiko Mizuno, Ryo Tatsukawa
    Applied Organometallic Chemistry 11 4 257 - 264 1997年 研究論文(学術雑誌) 
    Although organotins are notorious man-made organometallic species introduced into the aquatic environment, no investigation had been concerned with contamination of higher trophic animals such as marine mammals until the last few years. Our recent work demonstrated the detection of butyltin compounds (BTCs), including mono- (MBT), di-(DBT), and tri-butyltin (TBT) in marine mammals. This paper reviews BTC contamination in higher trophic animals, based on our recent publications. Analysis for BTCs showed significant accumulation in tissues and organs of three unless porpoises (Neophocaena phocaenoides) collected from Japanese coastal waters. More than 10 μg of butyltin ions per gram on a wet weight basis were detected in the liver of a porpoise collected in the semi-closed sea. Distribution of BTCs in the tissues and organs of the porpoises showed a similar pattern to several other marine mammal species: higher concentrations in liver and kidney, and lower in muscle and blubber. In addition, tissues and organs from two water birds and one sea turtle species were also analyzed for BTCs, and their concentrations and compositions were compared among the species. The results showed that the distribution of these contaminants extends widely, not only to marine mammals but also to other higher trophic species. On the other hand, the composition of the BTCs exhibited a specific profile in each species. The ratios of hepatic concentrations of DBT or MBT to TBT for marine mammals were relatively lower than those of water birds and the sea turtle, indicating that metabolism and excretion of TBT may be less efficient in the mammalian species. © 1997 by John Wiley & Sons, Ltd.
  • KS Guruge, S Tanabe, H Iwata, R Taksukawa, S Yamagishi
    ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 31 2 210 - 217 1996年08月 研究論文(学術雑誌) 
    Concentrations of butyltin compounds (BTs) were determined in various body tissues of common cormorants (Phalacrocorax carbo) collected from the Lake Biwa, Japan. Elevated concentrations of butyltins were detected in the feathers of cormorants. Among other organs and tissues, butyltin levels were also higher in the kidney (290 +/- 150 ng/g) and liver (270 +/- 260 ng/g), ranging from 115 to 544 ng/g and 142 to 1007 ng/g (wet wt basis), respectively. The accumulation of BTs in cormorant bodies was in the order of MBT > DBT > TBT and their organ specific burdens were in the order of muscle greater than or equal to feathers > skin > liver > rest of the tissues and organs. The higher levels of BTs residues in feather suggested the excretion of about one fourth of their body burden during a complete molting cycle, which has been a natural detoxification mechanism in these birds. Based on the whole body concentrations of BTs in cormorants (42-160 ng/g wet wt) and fish (10-55 ng/g wet wt) biomagnification factors were assessed to be in the range of 1.1-4.1. To our knowledge, this is the first fundamental study to substantially indicate the contamination and kinetics of BTs in wild birds.
  • Gi Beum Kim, Jong Su Lee, Shinsuke Tanabe, Hisato Iwata, Ryo Tatsukawa, Kenji Shimazaki
    Marine Pollution Bulletin 32 7 558 - 563 1996年 研究論文(学術雑誌) 
    The present study was conducted to elucidate the specific distribution of butyltin (BT) compounds in various tissues and organs of Steller sea lions collected from coastal waters of Hokkaido, Japan. BT concentrations were an order of magnitude higher in the liver than in other tissues and organs except hair, whereas organochlorine (OC) compounds accumulated at two to three orders of magnitude higher in blubber than in other tissues. No relationship was observed between BT concentrations and the lipid content in tissues, while the levels of OCs were positively associated with the lipid content. The levels of BTs in hair (1500 ng g-1 on a wet weight basis) were the highest of all the tissues analysed. Results also suggested that 26% of the total BT burden in the body was eliminated through shedding. Selective accumulation of BTs in liver and hair is attributed to its protein-binding capacity rather than lipophilicity. The discovery of high concentrations of BTs in hair implies their excretion by shedding in piliferous animals.
  • TANABE S, KUMARAN P, IWATA H, TATSUKAWA R, MIYAZAKI N
    Mar.Pollut.Bull. 32 1 27 - 31 1996年01月 研究論文(学術雑誌) 
    The enantiomeric ratio of α-hexachlorocyclohexane (α-HCH) in blubber of 10 species of adult male small cetaceans has been determined by means of capillary gas chromatography using β-cyclodextrin as a chiral stationary phase. The enantiomeric ratio of (+)-α-HCH/(-)-α-HCH ranged from 1.6 to 2.8, showing diverse values. Moreover, even in the same species, the ratios varied between animals collected from different localities. Dall's porpoise (Phocoenoides dalli) collected from the Bering Sea had enantiomeric ratios of 2.0-2.1 and others, from the North Pacific and Japan Sea, exhibited ratios ranging from 1.6-1.9. The ratios of β-HCH concentration to total HCH concentration (β-HCH/ΣHCH) was linearly related to the enantiomeric ratios of α-HCH (v = -0.46, p < 0.005). This may indicate that the metabolic capacity to degrade HCH isomers among cetaceans can be evaluated in terms of degradation of the (+)-α-HCH enantiomer. Present enantiomeric ratios were compared with earlier observations on various environmental samples and unbalanced degradation of (+)- and (-)-α-HCH enantiomers was suggested in small cetaceans.
  • K. S. Guruge, S. Tanabe, H. Iwata, R. Taksukawa, S. Yamagishi
    Archives of Environmental Contamination and Toxicology 31 2 210 - 217 1996年 研究論文(学術雑誌) 
    Concentrations of butyltin compounds (BTs) were determined in various body tissues of common cormorants (Phalacrocorax carbo) collected from the Lake Biwa, Japan. Elevated concentrations of butyltins were detected in the feathers of cormorants. Among other organs and tissues, butyltin levels were also higher in the kidney (290 ± 150 ng/g) and liver (270 ± 260 ng/g), ranging from 115 to 544 ng/g and 142 to 1007 ng/g (wet wt basis), respectively. The accumulation of BTs in cormorant bodies was in the order of MBT > DBT > TBT and their organ specific burdens were in the order of muscle ≤ feathers > skin > liver > rest of the tissues and organs. The higher levels of BTs residues in feather suggested the excretion of about one fourth of their body burden during a complete molting cycle, which has been a natural detoxification mechanism in these birds. Based on the whole body concentrations of BTs in cormorants (42-160 ng/g wet wt) and fish (10-55 ng/g wet wt) biomagnification factors were assessed to be in the range of 1.1- 4.1. To our knowledge, this is the first fundamental study to substantially indicate the contamination and kinetics of BTs in wild birds.
  • Iwata, H, Tanabe, S, Ueda, K, Tatsukawa, R
    Environmental Science and Technology 29 2 792 - 801 1995年03月 [査読有り]
  • K KANNAN, S TANABE, H IWATA, R TATSUKAWA
    ENVIRONMENTAL POLLUTION 90 3 279 - 290 1995年 研究論文(学術雑誌) 
    Concentrations of butyltin residues were determined in muscle tissue of fish collected from local markets and sea food shops in India, Bangladesh, Thailand, Indonesia, Vietnam, Taiwan, Australia, Papua New Guinea and the Solomon Islands. Contamination levels were determined in the Asia-Pacific region and human exposure was estimated. Similarly, corresponding liver samples of fish muscle collected in Australia, Papua New Guinea and the Solomon Islands were analyzed to obtain information on partitioning of butyltin compounds between muscle and liver tissues. Butyltin compounds were detected in most of the samples which suggested widespread contamination in Asia and Oceania. The concentrations of butyltin compounds were, on average, an order of magnitude higher in liver than in muscle. Residue concentration of Sigma butyltin in liver was found to be correlated significantly (p < 0.02) with those in muscle. Intensive ship-scrapping activities, sewage disposal and antifouling paints are considered the major sources of butyltins in this region. Increased proportions of MBT over DBT and TBT in samples from most locations indicated degradation of TBT to MBT in fish tissues during storage at 4 degrees C in the dark over 1-2 years. The possibility that fish have been subject to increased exposure to MBT and that TBT degrades to MBT quite rapidly in tropical environments are also considered. Butyltin concentrations in fish from Asia and Oceania were lower than those reported for Japan, Canada and the USA. Although the number of samples analyzed from each country was small, it is tentatively suggested that intake of butyltins by humans via consumption of fish in these countries was < 25% of the tolerable daily intake of 250 ng kg bw(-1) day(-1). To our knowledge, this is the first study reporting on butyltin pollution in developing Asian countries.
  • Hisato Iwata, Shinsuke Tanabe, Takahiko Mizuno, Ryo Tatsukawa
    Environmental Science and Technology 29 12 2959 - 2962 1995年 研究論文(学術雑誌) 
    Organotins are one of the most toxic chemicals in the aquatic environment. While contamination and toxic effects of organotin compounds in lower trophic aquatic organisms have been well-documented, no investigation has focused so far on higher aquatic organisms like marine mammals. We attempted to analyze butyltin compounds (BTCs), including mono-(MBTs), di-(DBTs), and tributyltin compounds (TBTs), in various tissues and organs of finless porpoise (Neophocaena phocaenoides) collected from Japanese coastal waters and detected these compounds in all the animals. The highest residue levels were found in the liver of a porpoise collected in the inland sea, recording more than 10 ppm BTCs on a wet weight basis. The composition of BTCs was different according to the tissues and organs with higher proportions of DBTs noticed in the liver and blood. Estimation of BTC burdens in tissues and organs indicated that muscle, liver, and blubber retained predominant portion of TBTs, DBTs, and MBTs. The occurrence of higher rates of TBTs on the whole implied the lower metabolic potential of porpoises to BTCs. © 1995, American Chemical Society. All rights reserved.
  • K KANNAN, Y YASUNAGA, H IWATA, H ICHIHASHI, S TANABE, R TATSUKAWA
    ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 28 1 40 - 47 1995年01月 研究論文(学術雑誌) 
    Concentrations of heavy metals, organochlorine pesticides, polychlorinated biphenyls and organotins were determined in horseshoe crabs, Tachypleus tridentatus, collected from Japanese coastal waters. Heavy metal concentrations were high in the hepatopancreas, gill and egg. Residue levels of heavy metals were comparable to those recorded in most benthic organisms from Japanese coastal waters. Organochlorine concentrations were detected at a few ng/g acid the residue pattern followed the order of polychlorinated biphenyls (PCBs) > chlordane compounds (CHLs) > hexachlorocyclohexanes (HCHs) > dichlorodiphenyltrichloroethane (DDTs) > hexachlorobenzene (HCB). Butyltin concentrations were high in the hepatopancreas, ranging from 350-2,270 ng/g in Hakata Bay and 570-5,000 ng/g (on a wet wt basis) in Habu Bay. Elevated concentrations of butyltins were also detected in the eggs of horseshoe crabs. High accumulations of butyltins in horseshoe crabs may pose a serious threat to their survival and therefore needs immediate attention to prevent their extinction.
  • Hisato Iwata, Shinsuke Tanabe, Kozo Ueda, Ryo Tatsukawa
    Environmental Science and Technology 29 3 792 - 801 1995年 研究論文(学術雑誌) 
    Contamination of semivolatile organochlorines (OCs) such as hexachlorobenzene (HCB), hexachlorocyclohexanes (HCHs), DDTs, chlordanes, and polychlorinated biphenyls (PCBs) was assessed in air, water, sediments, and soils from the Lake Baikal region, Russia. Comparison of the residue levels in the lake with those in other regions suggested the presence of local sources of DDTs and PCBs, although the residues were considered to be lower than those in the low-latitude areas in the eastern Asia and Oceania. Larger proportions of p,p'-DDT to total DDTs and similarities of PCB congener compositions to a Russian technical PCB formation were found in the samples analyzed, implying their usages nearby the lake. The estimated fluxes of OCs by gas exchange across the air-water interface applying the twofilm model indicated that the lake water plays a role as a sink for HCB, HCHs, and DDTs and also serves as a source for PCBs. The magnitude for PCB volatilization in this lake was found to be smaller than those in the Great Lakes for which the values have been previously reported. © 1995, American Chemical Society. All rights reserved.
  • S TANABE, H IWATA, R TATSUKAWA
    SCIENCE OF THE TOTAL ENVIRONMENT 154 2-3 163 - 177 1994年09月 研究論文(学術雑誌) 
    The present paper overviews the global contamination by persistent organochlorines and their ecotoxicological implications on marine mammals. The recent pattern of contamination by organochlorine residues in the coastal environment is prominent in tropical regions due to continuous usage in the low-latitude developing countries. The major emission source of organochlorines is probably the tropical belt and large quantities of volatilized contaminants are dispersed through the atmosphere on global terms. Reflecting this, a considerable contamination was observed in open ocean tropical waters as well as in the Arctic and nearby waters. The study of the mass transfer of organochlorines at the air-water interface suggests that the oceanic water bodies, particularly Arctic waters, act as a sink for persistent contaminants. In this regard, the marine mammals, particularly cetaceans, are one of the animal groups receiving high concentrations of persistent organochlorines arising out of a worldwide contamination. They can amplify much greater amounts of toxic contaminants through feeding and also pass them in large quantities from one generation to the next through lactation. Unfortunately, these animals have a smaller capacity for degradation of these contaminants due to the specific mode of cytochrome P-450 enzyme systems. These drug-metabolizing enzyme systems may be related to the possible effects of persistent organochlorines, particularly coplanar PCBs. Furthermore, the residue levels of these contaminants in marine mammals are unlikely to decline in the near future. Considering all these facts, it may be concluded that marine mammals are one of the most vulnerable and possible target organisms with regard to long-term toxicity of hazardous man-made chemicals in the future.
  • Hisato Iwata, Shinsuke Tanabe, Mari Aramoto, Norio Sakai, Ryo Tatsukawa
    Marine Pollution Bulletin 28 12 746 - 753 1994年 研究論文(学術雑誌) 
    Three surface sediments and two sediment cores were collected from the Gulf of Alaska, Bering Sea and Chukchi Sea, and analysed for persistent organochlorines (OCs). The geographical distributions of OCs showed different patterns according to their physicochemical properties. The concentrations of HCHs and HCB revealed rather uniform distribution, suggesting their more transportable nature in long-range atmospheric transport. On the other hand, DDTs and PCBs were predicted to be less transportable via the atmosphere due to the decreasing trends of residue levels in sediments from south to north. The OC profiles in the sediment core from the Gulf of Alaska which seemed to be preserved without turbation revealed the elevated residue levels from bottom to surface layers. This implies that the aerial inputs of OCs in the cold ocean are still continuing significantly. The accumulation rates of OCs into sediments were rather smaller than the atmospheric inputs, indicating that the residue levels in water bodies are unlikely to decrease rapidly in the near future. © 1994.
  • Hisato Iwata, Shinsuke Tanabe, Nobuyuki Miyazaki, Ryo Tatsukawa
    Marine Pollution Bulletin 28 10 607 - 612 1994年 研究論文(学術雑誌) 
    The blubber samples of eight species (12 specimens) of marine mammals caught between 1981 and 1993 in seas surrounding Japan and in the Indian, North Pacific and Antarctic Oceans, were analysed for butyltin compounds (BTCs). The column chromatography using dry florisil and acetonitrile enabled isolation of BTCs from lipids in fatty tissues like blubber, and led to the reliable analysis with efficient recoveries for these contaminants. BTCs were detected in all the animals except a minke whale from the Antarctic Ocean. The highest residue levels were found in a finless porpoise from the Seto-inland Sea, Japan with a BTC concentration of 770 ng g-1 on wet wt basis. Geographical distribution of the BTC concentrations in marine mammals showed a decreasing trend from the coastal to the open seas, indicating the presence of larger pollution sources nearby the coastal regions. Compositions of the BTCs in the blubber of finless porpoises seemed to be different from those found in aquatic organisms of lower trophic levels. Lower contributions of dibutyltins to the total BTCs in the blubber suggest the presence of their specific metabolic pathways. To our knowledge, this is the first report on the detection of BTCs in marine mammals. © 1994.
  • H IWATA, S TANABE, N SAKAI, A NISHIMURA, R TATSUKAWA
    ENVIRONMENTAL POLLUTION 85 1 15 - 33 1994年 研究論文(学術雑誌) 
    Persistent organochlorines in air, river water and sediment samples were analysed from eastern and southern Asia (India, Thailand, Vietnam, Malaysia, Indonesia) and Oceania (Papua New Guinea and Solomon Islands) to elucidate their geographical distribution in tropical environment. The concentrations of organochlorines in these abiotic samples collected from Taiwan, Japan and Australia were also monitored for comparison. Atmospheric and hydrospheric concentrations of HCHs (hexachlorocyclohexanes) and DDTs (DDT and its metabolites) in the tropical developing countries were apparently higher than those observed in the developed nations, suggesting extensive usage of these chemicals in the lower latitudes. CHLs (chlordane compounds) and PCBs (polychlorinated biphenyls) were also occasionally observed at higher levels in the tropics, implying that their usage area is also expanding southward. Distribution patterns of organochlorines in sediments showed smaller spatial variations on global terms, indicating that the chemicals released in the tropical environment are dispersed rapidly through air and water and retained less in sediments. The ratios of organochlorine concentrations in sediment and water phases were positively correlated with the latitude of sampling, suggesting that persistent and semivolatile compounds discharged in the tropics tend to be redistributed on a global scale.
  • Hisato Iwata, Shimsuke Tanabe, Ryo Tatsukawa
    Marine Pollution Bulletin 26 6 302 - 305 1993年 研究論文(学術雑誌)
  • Hisato Iwata, Shinsuke Tanabe, Norlo Sakal, Ryo Tatsukawa
    Environmental Science and Technology 27 6 1080 - 1098 1993年 研究論文(学術雑誌) 
    Concentrations of organochiorines such as hexachlorocyclohexanes (HCHs), DDTs, chlordanes, and PCBs were determined in the air and surface water from various oceans in 1989–1990, for understanding their recent distribution and the role of ocean in the long-range atmospheric transport and fate on global terms. The atmospheric concentrations were found to be still higher in the Northern Hemisphere than in the Southern Hemisphere, although the distribution pattern suggested the shift or expansion of their major sources from the mid to low latitudes during the last decade. In surface water, HCHs showed a considerable contamination over 40° N, whereas DDTs were higher near tropical Asia. Chlordanes and PCBs exhibited rather uniform distributions in both the hemispheres. Estimations of fluxes by gas exchange across the air-water interface gave insight into the dispersal of organochiorines through oceanic atmosphere depending on their Henry's law constants and the tendency of more transportable ones to deposit into the cold waters as an ultimate sink. © 1993, American Chemical Society. All rights reserved.
  • MS TABUCANON, S WATANABE, C SIRIWONG, R BOONYATUMANOND, S TANABE, H IWATA, R TATSUKAWA, S OHGAKI
    WATER SCIENCE AND TECHNOLOGY 25 11 17 - 24 1992年 研究論文(学術雑誌) 
    Water and sediment samples collected from the lower Chao Phraya River and a canal along the river during 1988 - 1991 were analyzed to determine the current status of contamination by organochlorine pesticides, such as HCHs, DDTs, aldrin, dieldrin and chlordanes. Aldrin and dieldrin had high frequencies of occurrence in water samples. The medians of concentrations of these pesticides were approximately one order of magnitude larger than total HCHs and total DDTs. Residue levels of these pesticides varied significantly. Relatively higher levels of aldrin were observed in the upstream; in contrast, residue levels of DDTs were higher in urban area. These phenomena seem to relate to the spraying purpose of these pesticides. Decreasing trends in the residue levels of pesticides during monitoring periods, however, were not observed clearly. Residue levels of organochlorines in the sediment samples were in the order of magnitude of PCBs, DDTs, chlordanes and HCHs.
  • S TANABE, A RAMESH, D SAKASHITA, H IWATA, R TATSUKAWA, D MOHAN, AN SUBRAMANIAN
    INTERNATIONAL JOURNAL OF ENVIRONMENTAL ANALYTICAL CHEMISTRY 45 1 45 - 53 1991年 研究論文(学術雑誌) 
    A HCH (BHC) application test was conducted in an experimental paddy field in the Vellar river watershed, Tamil Nadu state, South India. Interestingly, most of the HCH applied to the field was found to volatilize rapidly as low residue levels in water, rice plant and soil were recorded. After two weeks of an application, more than 90% of the HCH was found in the air and less than 10% in water, soil and rice plants, thus emphasizing that post-application volatilization is a major route for transport of insecticides to and through the atmosphere in tropical paddy areas. © 1991, Taylor & Francis Group, LLC. All rights reserved.
  • H. Takeoka, A. Ramesh, H. Iwata, S. Tanabe, A. N. Subramanian, D. Mohan, A. Magendran, R. Tatsukawa
    Marine Pollution Bulletin 22 6 290 - 297 1991年 研究論文(学術雑誌) 
    The residue levels of the insecticide HCH in Vellar estuary, Tamil Nadu, South India were surveyed along with the physical structure of estuary and its hydrokinetic parameters to assess the transport of contaminants in tropical coastal areas. From the flux model it was estimated that most of the HCH applied to the catchment area of Vellar river is removed to the air and only a small part of it was drained to the sea. Compared to the present situation, the flux of HCH to the sea seems to be much larger in the past when the river structure was different from the present. This implies that at present the localized contamination of HCH in the sea is reducing: instead more rapid contamination is advancing on global terms due to the 'long-range atmospheric transport' of residues from the 'point-source' areas. © 1991.
  • A RAMESH, S TANABE, H IWATA, R TATSUKAWA, AN SUBRAMANIAN, D MOHAN, VK VENUGOPALAN
    ENVIRONMENTAL POLLUTION 67 4 289 - 304 1990年 研究論文(学術雑誌) 
    Water samples collected from Vellar river and Pichavaran mangroves at Porto Novo (11° 29′ N, 79° 46′ E), Tamil Nadu State, South India, from December 1987 to January 1989 were analyzed to determine the seasonal variation of the levels of organochlorine insecticides such as HCH (BHC) and DDT. Both these insecticides showed higher levels from October to February, although this trend was more pronounced in HCH than DDT, reflecting the application of technical HCH largely and probably small quantities of DDT during the flowering season of rice. The α-HCH was detected as a dominant isomer for all seasons monitored followed by β-HCH Among DDT compounds, p, p′-DDT was the highest in river water except in the dry season when p,p′-DDD showed a higher percentage. On the other hand, in mangroves p,p′-DDE was highest during the wet season and p,p′-DDD during the dry season. Air-water partitioning data of HCH isomers and DDT compounds in Vellar river revealed that these chemicals tend to be in the water phase. These observations may aid in understanding the role of a tropical paddy area on the behavior and fate of man-made chemicals in view of worldwide contamination. © 1990.
  • S TANABE, H IWATA, Y KASHIWADA
    BULLETIN OF THE JSME-JAPAN SOCIETY OF MECHANICAL ENGINEERS 28 239 883 - 889 1985年 [査読有り]
     研究論文(学術雑誌)

書籍

  • 生物の科学 遺伝~死体に学ぶクジラ・イルカの秘密~
    落合真理・岩田久人 (範囲:人工化学物質による鯨類の汚染と影響)
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    朝倉書店 2011年
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    CRC Press 2010年
  • Interdisciplinary Studies on Environmental Chemistry vol. 3, Biological Responses to Contaminants: from Molecular to Community Level : Interindividual variation in arsenic metabolism in a Vietnamese population: association with 17 single nucleotide pol・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry vol. 3, Biological Responses to Contaminants: from Molecular to Community Level : Interindividual variation in arsenic metabolism in a Vietnamese population: association with 17 single nucleotide polymorphisms in AS3MT
  • Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Cytochrome P450 family 1 genes in Xenopus tropicalis
    TERRAPUB 2010年
  • Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral nervous system of dev・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral nervous system of developing red seabream (Pagrus major) embryos
  • Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Development of an in vitro reporter gene assay for screening the ecdysone receptor agonists in ・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Development of an in vitro reporter gene assay for screening the ecdysone receptor agonists in mysid crustacean
  • Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Molecular characterization of peroxisome proliferator-activated receptor isoforms from the baik・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Molecular characterization of peroxisome proliferator-activated receptor isoforms from the baikal seal (Pusa sibirica)
  • Interdisciplinary Studies on Environmental Chemistry, Vol. 3, Biological Responses to Chemical Contaminants: From Molecular to Community Level : Risk assessment of dioxins in wild birds by the combination of contamination level and species-specific res・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry, Vol. 3, Biological Responses to Chemical Contaminants: From Molecular to Community Level : Risk assessment of dioxins in wild birds by the combination of contamination level and species-specific response of aryl hydrocarbon receptor
  • Arsenic in Geosphere and Human Diseases : Methylation of inorganic arsenic and genetic polymorphisms in arsenic (+III oxidation state) methyltransferase in a Vietnamese population
    CRC Press 2010年
  • Interdisciplinary Studies on Environmental Chemistry vol. 3, Biological Responses to Contaminants: from Molecular to Community Level : Interindividual variation in arsenic metabolism in a Vietnamese population: association with 17 single nucleotide pol・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry vol. 3, Biological Responses to Contaminants: from Molecular to Community Level : Interindividual variation in arsenic metabolism in a Vietnamese population: association with 17 single nucleotide polymorphisms in AS3MT
  • Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Cytochrome P450 family 1 genes in Xenopus tropicalis
    TERRAPUB 2010年
  • Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral nervous system of dev・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral nervous system of developing red seabream (Pagrus major) embryos
  • Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Development of an in vitro reporter gene assay for screening the ecdysone receptor agonists in ・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Development of an in vitro reporter gene assay for screening the ecdysone receptor agonists in mysid crustacean
  • Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Molecular characterization of peroxisome proliferator-activated receptor isoforms from the baik・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Molecular characterization of peroxisome proliferator-activated receptor isoforms from the baikal seal (Pusa sibirica)
  • Interdisciplinary Studies on Environmental Chemistry, Vol. 3, Biological Responses to Chemical Contaminants: From Molecular to Community Level : Risk assessment of dioxins in wild birds by the combination of contamination level and species-specific res・・・
    TERRAPUB 2010年 
    Interdisciplinary Studies on Environmental Chemistry, Vol. 3, Biological Responses to Chemical Contaminants: From Molecular to Community Level : Risk assessment of dioxins in wild birds by the combination of contamination level and species-specific response of aryl hydrocarbon receptor
  • 分子でよむ環境汚染(鈴木 聡編)
    東海大学出版会 2009年
  • Persistent organic pollutants in Vietnam: environmental contamination and human exposure. Review of Environmental Contamination and Toxicology
    Springer 2008年
  • Persistent organic pollutants in Vietnam: environmental contamination and human exposure. Review of Environmental Contamination and Toxicology
    Springer 2008年
  • 化学物質の生態リスク評価と規制ー農薬編ー
    アイピーシー 2006年
  • Ecological Risk Assessment and Regulation of Chemical Substances-Agricultural Chemicals
    2006年
  • 水産学シリーズ140
    恒星社厚生閣刊 2004年
  • 微量人工化学物質の生物モニタリング 水産学シリーズ140
    恒星社厚生閣 2004年
  • 第7章 環境毒性
    「トキシコロジー」日本トキシコロジー学会教育委員会編、 朝倉書店 2002年
  • 海洋生態系と残留性有機汚染物質
    「海と環境:海が変わると地球が変わる」日本海洋学会 池田元美他編、 講談社 2001年
  • Contamination of the ecosystems of Lake Baikal by persistent organochlorines
    In: Minoura, K. editor. Lake Baikal; A mirror in time and space for understanding global change processes. The Netherland: Elsevier 2000年
  • Contamination of the ecosystems of Lake Baikal by persistent organochlorines
    In: Minoura, K. editor. Lake Baikal; A mirror in time and space for understanding global change processes. The Netherland: Elsevier 2000年
  • 環境影響評価法
    「毒性学-生体・環境・生態系-」(共著)、朝倉書店 1999年
  • 環境汚染物質の生態系への影響
    「毒性学-生体・環境・生態系-」(共著)、朝倉書店 1999年
  • 化学物質の動態
    「毒性学-生体・環境・生態系-」(共著)、朝倉書店 1999年
  • 環境毒性学の基本概念
    「毒性学-生体・環境・生態系-」(共著)、朝倉書店 1999年
  • ダイオキシン
    「毒性学-生体・環境・生態系-」(共著)、朝倉書店 1999年
  • PCB
    「沿岸の環境圏」(共著)、(株)フジ・テクノシステム 1998年
  • 有機塩素化合物による海洋汚染
    文明と環境 環境危機と現代文明 (共著)第11巻、朝倉書店 1996年
  • 石 弘之, 沼田 真, 湯浅 赳男, 守山 弘, 藤田 慎一, 小川 真理子, 河野 稠果, 河宮 信郎, 宇井 純, 岩田 久人, 立川 涼, 梅原 猛, 中村 玲子 
    朝倉書店 1996年 ISBN: 4254105614

講演・口頭発表等

  • Assessment of in vitro transactivation potencies of chicken estrogen receptor α by bisphenol analogs  [通常講演]
    Mayumi Sakata, Yuka Yoshinouchi, Haruhiko Nakata, Eun-Young Kim, Hisato Iwata
    第22回環境ホルモン学会研究発表会 2019年12月
  • Cardiovascular toxicity assessment of tris(2-chloroethyl)phosphate(TCEP) in ex-ovo chicken embryos  [通常講演]
    Kazuki Kanda, Shohei Ito, Dong-Hee Koh, Eun-Young Kim, Hisato Iwata
    第22回環境ホルモン学会研究発表会 2019年12月
  • Differences in POPs, Transcriptome and Proteome of Wild and Hatchery-Reared Baltic Salmons  [通常講演]
    Kanerva Mirella, Nguyen Tue, Kunisue Tatsuya, Vuori Kristiina, Iwata Hisato
    第22回環境ホルモン学会研究発表会 2019年12月
  • Sex-dependent disruption of lipid homeostasis in rat offspring by prenatal bisphenol A exposure  [通常講演]
    Hoa Thanh Nguyen, Kimika Yamamoto, Midori Iida, Tetsuro Agusa, Mari Ochiai, Lingyun Li, Akifumi Eguchi, Kurunthachalam Kannan, Eun-Young Kim, Hisato Iwata
    第22回環境ホルモン学会研究発表会 2019年12月
  • Ex-ovoニワトリ胚におけるリン酸トリス(2-クロロエチル)(TCEP)の発生毒性評価  [通常講演]
    Kazuki Kanda, Shohei Ito, Dong-Hee Koh, Eun-Young Kim, Hisato Iwata
    3rd International Chemical Hazard Symposium 2019年09月
  • 残留性有機汚染物質による鯨類の汚染と培養細胞を用いた毒性影響評価  [招待講演]
    落合真理,川邊陸,田島木綿子,山田格,栗原望,国末達也,岩田久人
    第25回日本野生動物医学会大会 2019年08月
  • Assessment of the effects of 1,3,7-TriBDD exposure on developing chicken embryos by hepatic transcriptome analysis  [通常講演]
    Jae Gon Park, Hisato Iwata, Hoa Thanh Nguyen, Tatsuya, Kunisue, Eun-Young Kim
    39th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2019) 2019年08月
  • Isoform- and ligand-specific activities of AHR and ARNT pairs in the chicken  [通常講演]
    Dong-Hee Koh, Ji-Hee Hwang, Jae-Gon Park, Woo-Seon Song, Hisato Iwata, Eun-Young Kim
    39th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2019) 2019年08月
  • Cardiotoxicity assessment of tris[2-chloroethyl] phosphate [TCEP] in ex-ovo chicken embryos by in situ observation and transcriptome analysis  [通常講演]
    Kazuki Kanda, Shohei Ito, Dong-Hee Koh, Eun-Young Kim, Hisato Iwata
    39th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2019) 2019年08月
  • Effects of prenatal exposure to bisphenol A in rat offspring: assessment by multi-omics analyses  [通常講演]
    Hoa Thanh Nguyen, Kimika Yamamoto, Midori Iida, Tetsuro Agusa, Mari Ochiai, Lingyun Li, Akifumi Eguchi, Kurunthachalam Kannan, Eun-Young Kim, Hisato Iwata
    39th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2019) 2019年08月
  • In silico prediction of the metabolism of PCB congeners by cytochrome P450 isozymes in Yusho patients  [通常講演]
    Shusaku Hirakawa, Takashi Miyawaki, Tsuguhide Hori, Jumboku Kajiwara, Susumu Katsuki, Masashi Hirano, Yuka Yoshinouchi, Hisato Iwata, Chikage Mitoma, Masutaka Furue
    39th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2019) 2019年08月
  • Introduction on Ehime Univ. Research Group: Strategy for establishing AOP in wildlife  [通常講演]
    Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Assessment of developmental toxicity of imidacloprid using chicken embryos in shell-less culture system  [通常講演]
    Takara Fukunaga, Kazuki Kanda, Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Evaluation of CYP1A1, 1A2 and 1B1 induction in TCDD-exposed finless porpoise fibroblasts  [通常講演]
    Kohei Morita, Mari Ochiai, Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Effects of exposure to organochlorine compounds on testicular proteome of baleen whales  [通常講演]
    Tomomasa Taniyama, Thanh Hoa Nguyen, Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • In vitro assessment of chicken estrogen receptor transactivation by bisphenol analogs  [通常講演]
    Mayumi Sakata, Yuka Yoshinouchi, Haruhiko Nakata, Eun-Young Kim, Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Developmental effects of exposure to tris (2-chloroethyl) phosphate (TCEP) on chicken embryos by in situ observation and transcriptome analysis  [通常講演]
    Kazuki Kanda, Shohei Ito, Dong-Hee Koh, Eun-Young Kim, Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Evaluation of effects of oxytetracycline (OTC) on the immune system in red seabream (Pagrus major)  [通常講演]
    Su-Min Bak, Fumiya Takahashi, Suzuki Satoru, Eun-Young Kim, Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Transcriptomic profiling of 1,3,7-TriBDD exposure in developing chicken embryo liver  [通常講演]
    Jae Gon Park, Hisato Iwata, Nguyen Minh Tue, Tatsuya Kunisue, Eun-Young Kim
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Multi-omics analyses reveal mechanisms of action of prenatal bisphenol A exposure in rat offspring  [通常講演]
    Hoa Thanh Nguyen, Kimika Yamamoto, Midori Iida, Tetsuro Agusa, Mari Ochiai, Lingyun Li, Rajendiran Karthikraj, Eguch Akifumi, Kurunthachalam Kannan, Eun-Young Kim, Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Differences in POPs, transcriptome and proteome of wild and hatchery-reared Baltic salmons  [通常講演]
    Kanerva Mirella, Nguyen Tue, Kunisue Tatsuya, Vuori Kristiina, Iwata Hisato
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Cytotoxicity and proteomics analyses of POPs using cetacean fibroblasts  [通常講演]
    Mari Ochiai, Nozomi Kurihara, Ayaka Matsuda, Takashi Matsuishi, Shin Nishida, Kunisue Tatsuya, Hisato Iwata
    1st Korea-Japan Joint Symposium on Adverse Outcome Pathways 2019年07月
  • Ecotoxicology of aquatic mammals: in vitro and in silico approaches to predict the chemical-induced disruption of nuclear receptor signaling pathways  [招待講演]
    Hisato Iwata
    9th International conference on Marine Pollution and Ecotoxicology 2019年06月 口頭発表(招待・特別)
  • Cetacean cells as a tool for risk assessment of environmental pollutants  [招待講演]
    Mari Ochiai, Nozomi Kurihara, Shusaku Sawa, Shuichi Iwata, Kunisue Tatsuya, Hisato Iwata
    International Symposium-Workshop 2019 Scientific Studies of Marine Mammals in Asia 2019年06月
  • スナメリ (Neophocaena asiaeorientalis sunameri) における染色体の種内変異に関する予備的研究  [通常講演]
    栗原望,中田章史,落合真理,岩田久人
    日本セトロジー研究会東京大会 2019年06月
  • Differences in POPs, Transcriptome and Proteome of Wild and Hatchery-Reared Baltic Salmons  [通常講演]
    Mirella Kanerva, Tue Nguyen, Tatsuya Kunisue, Kristiina Vuori, Hisato Iwata
    SETAC Europe 29th Annual Meeting 2019年05月
  • In vitro and in silico evaluations of binding affinities of pereluoroalkyl substances to baikal seal peroxisome proliferator-activated receptor A  [通常講演]
    Hiroshi Ishibashi, Masashi Hirano, Eun-Young Kim, Hisato Iwata
    20th Pollutant Responses In Marine Organisms-PRIMO20 2019年05月
  • Effects of exposure to tris (2-chloroethyl) phosphate (TCEP) on chicken embryos: in situ observation in a shell-less incubation system  [通常講演]
    Kazuki Kanda, Shohei lto, Dong-Hee Koh, Eun-Young Kim, Hisato Iwata
    環境ホルモン学会 第21回研究発表会 2018年12月
  • Implication of obesogenic effects of prenatal bisphenol A exposure on rat offspring by multi-omics analysis  [通常講演]
    Hoa Thanh Nguyen, Kimika Yamamoto, Midori Iida, Tetsuro Agusa, Mari Ochiai, Lingyun Li, Kurunthachalam Kannan, Eun-Young Kim, Hisato Iwata
    環境ホルモン学会 第21回研究発表会 2018年12月
  • Hepatic proteome profiling in cane toad [rhinella marina] from the Philippines  [通常講演]
    Rosal, J. J, Tsuchiya, M. C, Agusa, T, Hirano, M, Iwata, H
    SETAC AP 2018 2018年09月
  • Characterization of the hepatic transcriptome in chicken AHR2 transgenic mice  [通常講演]
    Park, J-G, Nomura, K, Iwata, H, Kim, E-Y
    SETAC AP 2018 2018年09月
  • Effects of exposure to tris [2-chloroethyl] phosphate [tcep] on chicken embryos in the shell-less incubation system  [通常講演]
    Kanda, K, Ito, S, Koh, D-H, Kim, E-Y, Iwata, H
    SETAC AP 2018 2018年09月
  • Evaluation of sensitivity of dioxin related chemicals to polar bear [ursus maritimus] AHR  [通常講演]
    Hwang, J-H, Kannan, K, Evans, T. J, Iwata, H, Kim, E-Y
    SETAC AP 2018 2018年09月
  • In vitro and in silico ahr assays for assessing the risk of heavy oilcontaminated marine fish  [通常講演]
    Bak, S. M, Nakata, H, Koh, D-H, Yoo, J, Iwata, H, Kim, E-Y
    SETAC AP 2018 2018年09月
  • Differences in POPs and transcriptomes of wild and hatchery-reared baltic salmons  [通常講演]
    Kanerva, M, Nguyen, M. T, Kunisue, T, Amvuori, K, Iwata, H
    SETAC AP 2018 2018年09月
  • Effect of prenatal bisphenol a exposure on the hepatic transcriptome in chicken embryos: understanding of sexspecific effects  [通常講演]
    Ito, S, Iida, M, Nguyen, H.T, Agusa, T, Hirano, M, Ochiai M, Kim, E-Y, Iwata, H
    SETAC AP 2018 2018年09月
  • Structure-activity relationships of Baikal seal estrogen receptors and environmental phenols  [通常講演]
    Yoshinouchi Y, Hirano M, Nakata H, Nomiyama K, Tanabe S, Kim E-Y, Iwata H
    EUROTOX2018 2018年09月
  • In vitro cytotoxicity assessments of persistent organic pollutants using cetacean fibroblasts  [通常講演]
    Ochiai M, Kurihara N, Matsuda A, Nakagun S, Shiozaki A, Nakata A, Matsuishi T, Kunisue T, Iwata H
    EUROTOX2018 2018年09月
  • PCBs as an environmental obesogen in dogs: evidence from hepatic transcriptome, metabolome, and lipidome analyses  [通常講演]
    Tamura S, Agusa T, Hirano M, Eguchi A, Nomiyama K, Li L, Kannan K, Tanabe S, Kim EY, Iwata H
    Dioxin2018 2018年08月
  • In vitro and in silico approaches for assessing the activation of Baikal seal estrogen receptors by bisphenols and OH-PCBs  [通常講演]
    Yoshinouchi Y, Hirano M, Nakata H, Nomiyama K, Tanabe S, Kim EY, Iwata H
    Dioxin2018 2018年08月
  • Evaluating estrogenic and anti-estrogenic potency of bisphenol A analogues in vivo and in silico using zebrafish  [通常講演]
    Kubota A, Wakayama Y, Lee JS, Nakamura M, Kawai Y, Yoshinouchi Y, Iwata H, Hirano M, Nakata H
    Dioxin2018 2018年08月
  • Develop of in silico computational method for seeking the PPARγ ligand  [通常講演]
    Koh D-H, Song W-S, Hwang J-H, Iwata H, Kim E-Y
    Dioxin2018 2018年08月
  • IN SITU OBSERVATIN OF CHICKEN EMBRYOS TREATED WITH TRIS(2-CHLOROETHYL) PHOSPHATE(TCEP) IN THE SHELL-LESS INCUBATION SYSTEM  [通常講演]
    Kazuki Kanda, Shohei Ito, Dong-Hee Koh, Eun-Young Kim, Hisato Iwata
    SETAC Japan 2018年 年会 2018年07月
  • Molecular Mechanisms Underlying Species Differences in Transactivation Potencies of Seal and Dog Estrogen Receptors by OH-PCBs  [通常講演]
    Yuka Yoshinouchi, Hiroki Okuda, Masashi Hirano, Kei Nomiyama, Shinsuke Tanabe, Kim Eun-Young, Hisato Iwata
    SOT 57th Annual Meeting and ToxExpo 2018年03月
  • Predicted Adverse Outcome Pathways of Prenatal Exposure to Triclosan in Chicken Embryos  [通常講演]
    Jiahua Guo, Shohei Ito, Hoa Thanh Nguyen, Kimika Yamamoto, Rumi Tanoue, Tatsuya Kunisue, Hisato Iwata
    SOT 57th Annual Meeting and ToxExpo 2018年03月
  • In Silico Prediction and In Vivo Measurement of Estrogen-Like Effects of Bisphenol Analogues in Zebrafish  [通常講演]
    Akira Kubota, Y. Wakayama, M. Nakamura, Y. Kawai, Yuka Yoshinouchi, Hisato Iwata, Masashi Hirano, H. Nakata
    SOT 57th Annual Meeting and ToxExpo 2018年03月
  • Transcriptome Analysis Reveals the Mechanism of Transgenerational Effects of Bisphenol A in Rats  [通常講演]
    Hoa Thanh Nguyen, Kimika Yamamoto, Midori Iida, Tatsuya Agusa, Masashi Hirano, Mari Ochiai, Kim Eun-Young, Hisato Iwata
    SOT 57th Annual Meeting and ToxExpo 2018年03月
  • Hepatic Transcriptome Analysis to Assess the Effects of Prenatal Bisphenol A Exposure on Developing Chicken Embryos  [通常講演]
    Shohei Ito, Midori Iida, Hoa Thanh Nguye, Tetsuro Agusa, Masashi Hirano, Mari Ochiai, Kim Eun-Young, Hisato Iwata
    SOT 57th Annual Meeting and ToxExpo 2018年03月
  • ハンドウイルカの培養細胞を用いた環境汚染物質の免疫・細胞毒性影響評価  [通常講演]
    落合真理, 西田悠輝, 澤 修作, 岩田秀一, 中郡 翔太郎, 岩田久人
    第二回つくみイルカ研究シンポジウム 2018年01月
  • ゼブラフィッシュをモデルとしたin silicoおよびin vivo解析によるビスフェノール類のエストロゲン様作用の評価  [通常講演]
    久保田彰, 若山裕己, 中村倫子, 川合佑典, 芳之内結加, 岩田久人, 平野将司, 中田晴彦
    第20回環境ホルモン学会 2017年12月
  • イヌ・アザラシ・マウスのエストロゲン受容体転写活性化能の種差を規定する分子機序  [通常講演]
    芳之内結加, 奥田博貴, 平野将司, 野見山桂, 田辺信介, 金恩英, 岩田久人
    第20回環境ホルモン学会 2017年12月
  • Hepatic transcriptome profiles of rats exposed to bisphenol A during pregnancy (2017): comparison with those of their offspring  [通常講演]
    Nguyen, H. T, Yamamoto, K, Iida, M, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    第20回環境ホルモン学会 2017年12月
  • ビスフェノールAの出生前暴露によるニワトリ新生雛の肝臓トランスクリプトームへの影響の雌雄差  [通常講演]
    伊藤匠平, 飯田緑, Thanh Nguyen Hoa, 阿草哲郎, 平野将司, 落合真理, 金恩英, 岩田久人
    第20回環境ホルモン学会 2017年12月
  • Hazard assessment of triclosan predicted from the liver transcriptome in chicken embryos  [通常講演]
    Guo, J, Ito, S, Nguyen, H. T, Yamamoto, K, Tanoue, R, Kunisue, T, Iwata, H
    第20回環境ホルモン学会 2017年12月
  • Persistent organic pollutants (POPs) in dolphin species -Species- and tissue-specific accumulation-  [通常講演]
    Ochiai, M, Isobe, T, Tajima, Y, Yamada, T. K, Nomiyama, K, Kunisue, T, Iwata, H, Tanabe, S
    10th International Meeting of Asian Society of Conservation Medicine 2017年09月
  • Transcriptome analysis to assess the effects of prenatal bisphenol A exposure on developing chicken embryos  [通常講演]
    Ito, S, Iida, M, Nguyen, H. T, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    The International Symposium on Persistent Toxic Substances (ISPTS2017) 2017年09月
  • Gender and life stage defferences in effects of prenatal exposure to bisphenol A on the liver transcriptome of rat offspring  [通常講演]
    Nguyen, H. T, Yamamoto, K, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    The International Symposium on Persistent Toxic Substances (ISPTS2017) 2017年09月
  • Effects on hepatic transcriptome and metabolome in beagle dogs treated with PCBs  [通常講演]
    Tamura, S, Agusa, T, Hirano, M, Eguchi, A, Nomiyama, K, Tanabe, S, Kim, E. Y, Iwata, H
    The International Symposium on Persistent Toxic Substances (ISPTS2017) 2017年09月
  • Transgenerational effects of bisphenol a on liver transcriptome of rat offspring  [通常講演]
    Nguyen, H. T, Yamamoto, K, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    Vietnam – Japan Scientific Exchange Meeting 2017 2017年09月
  • 水酸化PCBsによるアザラシ・イヌエストロゲン受容体転写活性可能の評価  [通常講演]
    芳之内結加, 奥田博貴, 平野将司, 野見山桂, 田辺信介, 金恩英, 岩田久人
    第44回日本毒性学会学術年会 2017年07月
  • 飼育下のハンドウイルカ(Tursiops truncatus)のリンパ球を用いた環境汚染物質による免疫毒性評価  [通常講演]
    西田悠輝, 落合真理, 澤修作, 岩田秀一, 岩田久人
    第28回日本セトロジー研究会(札幌)大会 2017年06月
  • 鯨類由来線維芽細胞を用いた環境汚染物質の毒性影響評価  [通常講演]
    落合真理, 栗原望, 松田純佳, 中郡翔太郎, 塩崎彬, 中田章史, 松石隆, 国末達也, 岩田久人
    第28回日本セトロジー研究会(札幌)大会 2017年06月
  • Effects of pops on the lymphocyte proliferation of captive bottlenose dolphins (tursiops truncatus)  [通常講演]
    Nishida, Y, Ochiai, M, Sawa, S, Iwata, S, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Effects of pcb-exposure on thyroid hormone homeostasis of dogs and cats  [通常講演]
    Takaguchi, K, Nomiyama, K, Nishikawa, H, Mizukawa, H, Tanoue, R, Yoshinouchi, Y, Yokoyama, N, Ichii, O, Takiguchi, M, Nakayama, S, Ikenaka, Y, Ishizuka, M, Iwata, H, Kunisue, T, Tanabe, S
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Identification of cytochrome p450 gene families in the liver transcriptome of baikal seals (pusa sibirica)  [通常講演]
    Tsuchiya, M. C, Aquino, G. M, Kim, E. Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Identification of ahr signaling pathways affected by tcdd exposure in red seabream embryos  [通常講演]
    Iida, M, Fujii, S, Uchida, M, Nakamura, H, Kagami, Y, Agusa, T, Hirano, M, Bak, S. M, Kim, E. Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Liver transcriptome changes by exposure to 4-oh-cb107 in male wistar rats  [通常講演]
    Iida, M, Ochiai, M, Agusa, T, Fujii, S, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Effects of in vivo exposure to pcbs on hepatic transcriptome and metabolome in beagle dogs  [通常講演]
    Tamura, S, Agusa, T, Hirano, M, Eguchi, A, Nomiyama, K, Tanabe, S, Kim, E. Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Developmental effects of prenatal exposure to bisphenol a on the hepatic transcriptome in chicken embryos  [通常講演]
    Ito, S, Iida, M, Nguyen, H. T, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Effects of prenatal exposure to triclosan on the liver transcriptome in chicken embryos  [通常講演]
    Guo, J, Ito, S, Nguyen, H. T, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Hepatic proteome analysis of nile tilapias from philippines contaminated with pops  [通常講演]
    Legaspi, B. C. L, Tsuchiya, M. C, Hirano, M, Agusa, T, Matsuoka, J, Kunisue, T, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • In silico and in vitro screening of the effects of ppcps on mysid ecdysteroid receptor signaling  [通常講演]
    Hirano, M, Ohno, Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Species differences in transactivation potencies of seal and dog estrogen receptors by hydroxylated pcbs  [通常講演]
    Yoshinouchi, Y, Okuda, H, Hirano, M, Nomiyama, K, Tanabe, S, Kim, E. Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Assessment of heavy oil-derived pahs for red seabream ahr activation by in silico and in vitro approaches  [通常講演]
    Bak, S. M, Nakata, H, Iwata, H, Kim, E. Y
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Molecular structural analysis of specific ligand activity of polar bear (ursus maritimus) ahr  [通常講演]
    Hwang, J, Kannan, K, Evans, T. J, Iwata, H, Kim, E. Y
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • In vivo and in silico assessment of estrogen-like effects of bisphenol analogues in zebrafish  [通常講演]
    Wakayama, Y, Nakamura, M, Morita, Y, Yoshinouchi, Y, Iwata, H, Hirano, M, Nakata, H, Kawai, Y, Kubota, A
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Effects of prenatal exposure to bisphenol a on the liver weight and hepatic gene expression in rat offspring  [通常講演]
    Yamamoto, K, Nguyen, H. T, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Hepatic transcriptome responses to bisphenol a prenatal exposure in rat offspring  [通常講演]
    Nguyen, H. T, Yamamoto, K, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Risk assessment of triclosan in the global environment using a probabilistic approach  [通常講演]
    Guo, J, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Neurotoxicity assessment of environmental contaminats with chemically-induced neurons of dolphins  [通常講演]
    Ochiai, M, Nguyen, H. T, Kurihara, N, Hirano, M, Murakami, Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Structure-activity relationships of baikal seal estrogen receptors and environmental pollutants  [通常講演]
    Yoshinouchi, Y, Hirano, M, Nakata, H, Nomiyama, K, Tanabe, S, Kim, E. Y, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Auto-induction mechanism of aryl hydrocarbon receptor 2 gene by tcdd-activated ahr1 and ahr2 in the red seabream  [通常講演]
    Bak, S. M, Iida, M, Soshilov, A. A, Denison, M. S, Iwata, H, Kim, E. Y
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Effects of a naturally synthesized dioxin, 1, 3, 7-tribromodibenzo-p-dioxin on the mysid transcriptome  [通常講演]
    Hirano, M, Uchida, M, Arizono, K, Iwata, H
    19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19) 2017年06月
  • Effects of prenatal exposure to bisphenol A on hepatic transcriptome at different life stages of rat offspring  [通常講演]
    Nguyen, T. H, Yamamoto, K, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    環境ホルモン学会 第19回研究発表会 2016年12月
  • ビスフェノールAの出生前曝露によるラット新生仔の体重・肝重量と肝遺伝子発現への影響  [通常講演]
    山本 季美花, Nguyen Thanh Hoa, 阿草哲郎, 平野将司, 落合真理, 金 恩英, 岩田久人
    環境ホルモン学会 第19回研究発表会 2016年12月
  • In silico/in vitro analyses of the interaction of avian AHR and natural ligands  [通常講演]
    Koh, D. H, Iwata, H, Kim, E. Y
    環境ホルモン学会 第19回研究発表会 2016年12月
  • Molecular characterization of aryl hydrocarbon receptor (AHR) in Polar bears (Ursus maritimus)  [通常講演]
    Hwang, J. H, Kannan, K, Evans, T. J, Iwata, H, Kim, E. Y
    環境ホルモン学会 第19回研究発表会 2016年12月
  • ビスフェノールAの出生前曝露によるニワトリ新生雛の肝臓トランスクリプトームへの影響  [通常講演]
    伊藤匠平, 阿草哲郎, 平野将司, 落合真理, 金 恩英, 岩田久人
    環境ホルモン学会 第19回研究発表会 2016年12月
  • PCBsのin vitro曝露によるビーグル犬の肝トランスクリプトームとメタボロームへの影響  [通常講演]
    田村沙弥, 阿草哲郎, 平野将司, 江口哲史, 野見山桂, 田辺信介, 金 恩英, 岩田久人
    環境ホルモン学会 第19回研究発表会 2016年12月
  • Structural characteristics of avian aryl hydrocarbon receptors to decipher dioxin susceptibility and ecological factors related to their genotypes  [通常講演]
    Hwang, J. H, Park, H. J, Bak, S. M, Hirano, M, Iwata, H, Park, J. Y, Park Y. S, Kim, E. Y
    環境ホルモン学会 第19回研究発表会 2016年12月
  • Auto-induction mechanism of aryl hydrocarbbon receptor 2 (AHR2) gene by AHR1 and AHR2 in the red seabream  [通常講演]
    Bak, S. M, Iida, M, Soshilov, A. A, Denison, M. S, Iwata, H, Kim, E. Y
    環境ホルモン学会 第19回研究発表会 2016年12月
  • メタボローム解析を用いたベトナムの地下水ヒ素汚染地域住民の影響評価:第2報  [通常講演]
    阿草哲郎, 江口哲史, 國頭 恭, Tue, N. M, Lan, V. T. M, Minh, T. B, Trang, P. T. K, 高橋 真, Viet, P. H, 田辺信介, 岩田久人
    第22回ヒ素シンポジウム 2016年11月
  • In vitro and in silico assessment of cytochrome P450-dependent biotransformation capacity of PCBs in the Caniformia; the Baikal seal vs the beagle dog  [通常講演]
    Iwata, H, Yoo, J, Tamura, S, Hirano, M, Nomiyama, K, Tanabe, S, Kim, E. Y
    SETAC North America 37th Annual Meeting 2016年11月
  • Cross omics analysis for PCBs toxicity in the dog brain-Effect on mitochondrial functions-  [通常講演]
    Takaguchi, K, Nomiyama, K, Lauan, C. M, Yoo, J, Mizukawa, H, Iwata, H, Kunisue, T, Tanabe, S
    SETAC North America 37th Annual Meeting 2016年11月
  • Sex-dependent effects of prenatal bisphenol A exposure on liver transciptome of rat offspring  [通常講演]
    Thanh, N. H, Agusa, T, Hirano, M, Ochiai, M, Kim, E.Y, Iwata, H
    SETAC North America 37th Annual Meeting 2016年11月
  • Next generation sequencing analysis to assess the effects of prenatal bisphenol A exposure on developing chicken embryos  [通常講演]
    Itoh, S, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    SETAC North America 37th Annual Meeting 2016年11月
  • Hepatic proteome to accoun for the molecular mechanism underlying dioxin susceptibility in C2H/Ipr and MRL/Ipr mouse strains  [通常講演]
    Thanh, N. H, Lauan, M. C, Yoo, J, Iida, M, Agusa, T, Kim, E. Y, Iwata, H
    SETAC North America 37th Annual Meeting 2016年11月
  • Hepatic transcriptome analysis to assess the effects of polychlorinated biphenyls on beagle dogs  [通常講演]
    Tamura, S, Agusa, T, Hirano, M, Eguchi, A, Nomiyama, K, Tanabe, S, Kim. E. Y, Iwata, H
    The 9th International PCB Workshop 2016年10月
  • Risk assessment of disruption of estrogen receptor signaling pathway by OH-PCBs in Baikal seals; application of in vitro and in silico approaches  [通常講演]
    Yoshinouchi, Y, Hirano, M, Nomiyama, K, Tanabe, S, Kim, E. Y, Iwata, H
    The 9th International PCB Workshop 2016年10月
  • Disruption of mitochondrial functions by PCB exposure in the dog brain: Toxicological assessment using cross omics  [通常講演]
    Takaguchi, K, Nomiyama, K, Eguchi, A, Claret, L. M, Kusaki, M, Yoo, J, Mizukawa, H, Iwata, H, Kunisue, T, Tanabe, S
    The 9th International PCB Workshop 2016年10月
  • Toxicological assessment of PCBs and OH-PCBs in the brain of dogs using metabolomics approach  [通常講演]
    Nomiyama, K, Takaguchi, K, Eguchi, A, Mizukawa, H, Yoo, J, Tamura, S, Oshihoi, T, Iwata, H, Kunisue, T, Tanabe, S
    The 9th International PCB Workshop 2016年10月
  • Accumulation prperties of polychlorinted biphenyl cogeners in Yusho patients and assessment of their cytochrome P450-dependent metabolism by in silico docking simulation  [通常講演]
    Hirakawa S, Miyawaki, T, Hori, T, Kajiwara, J, Susumu, K, Hirano, M, Iwata, H, Masutaka, F
    The 9th International PCB Workshop 2016年10月
  • 水酸化PCBsによるバイカルアザラシ エストロゲン受容体を介した影響評価 -In vitro・in silico法を用いたアプローチ-  [通常講演]
    芳之内 結加, 平野将司, 野見山 桂, 田辺信介, 金 恩英, 岩田久人
    第22回日本環境毒性学会研究発表会 2016年09月
  • Hepatic proteome analysis of dioxin-sensitive and -resistant mice exposed to 2,3,7,8-tetrabromodibenzo-p-dioxin  [通常講演]
    Thanh, H. N, Lauan, M. C, Yoo, J, Iida, M, Agusa, T, Hirano, M, Kim, E. Y, Iwata, H
    15th Human Proteome Organization World Congress (HUPO 2016 Taipei) 2016年09月
  • Contamination by trace elements associated with e-waste recycling processes in developing countries  [通常講演]
    Agusa, T, Takigami, H, Fujimori, T, Eguchi, A, Bekki, K, Yoshida, A, Terazono, A, Ha, N. N, Asante, K. A, Biney, C. A, Agyekum, W. A, Bello, M, Ramu, K, Ballesteros Jr, F. C, Bulbule, K. A, Parthasaraty, P, Takahashi, S, Subramanian, A, Iwata, H, Tanabe, S
    2016 1st Eastern Asia Conference for Sustainable Economy (EACSE) 2016年09月
  • In vitro and in silico approaches for assessing the activation of Baikal seal estrogen receptors by OH-PCBs  [通常講演]
    Yoshinouchi, Y, Hirano, M, Nomiyama, K, Tanabe, S, Kim, E. Y, Iwata, H
    36th International Symposium on Halogenated Persistent Organic Pollutants 2016年08月
  • The aryl hydrocarbon receptor signaling pathway in the red seabream  [通常講演]
    Iwata, H, Bak, S. M, Iida, M, Kim, E. Y
    6th Joint Forum of Environnmental Sciences 2016年08月
  • 酸化PCBsによるバイカルアザラシ エストロゲン受容体 転写活性化能とその分子機構
    芳之内結加, 平野将司, 野見山 桂, 田辺信介, 金 恩英, 岩田久人
    第25回環境化学討論会 2016年06月
  • メタボロミクスアプローチを用いたイヌ脳へのOH-PCBs 毒性機序の解明  [通常講演]
    野見山 桂, 高口倖暉, 江口哲史, 水川葉月, Jean, Y, 田村沙弥, 忍穂井 智子, 岩田久人, 国末達也, 田辺信介
    第25回環境化学討論会 2016年06月
  • クロスオミックスによるイヌ脳へのPCBs 毒性評価:ミトコンドリア機能へ及ぼす影響解析  [通常講演]
    高口倖暉, 野見山 桂, Claret, L. M, 草木桃子, Jean, Y, 水川葉月, 岩田久人, 国末達也, 田辺信介
    第25回環境化学討論会 2016年06月
  • 茨城県に集団座礁したカズハゴンドウ(Peponocephala electra)に残留するPCBs, OH-PCBsの脳内負荷量と母仔間移行  [通常講演]
    落合真理, 野見山桂, 磯部友彦, 山田格, 田島木綿子, 岩田久人, 国末達也, 田辺信介
    第27回日本セトロジー研究会 2016年06月
  • メタボロミクスを用いたヒ素汚染地域住民の影響評価  [通常講演]
    阿草哲郎, 江口哲史, Tue, N.M, Lan, V. T. M, Minh, T. B, Trang, P. T. K, 高橋 真, Viet, P. H, 田辺信介, 岩田久人
    第25回環境化学討論会 2016年06月
  • 水酸化PCBsによるバイカルアザラシ エストロゲン受容体転写活性化能とその分子機構  [通常講演]
    芳之内結加, 平野将司, 野見山 桂, 田辺信介, 金 恩英, 岩田久人
    第25回環境化学討論会 2016年06月
  • メコン川および紅河流域における地下水のヒ素汚染  [通常講演]
    阿草哲郎, 岩田久人, 井上 英, Karri Ramu, Nguyen Minh Tue, 田辺信介, 國頭 恭, 久保田 領志, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, Nguyen Ngoc Ha, Nguyen Phuc Cam Tu, Bui Cach Tuyen, Paromita Charaborty, Chhoun Chamnan, Alissara Reungsang, Kriengsak Srisuk, 中村 哲, 滝沢 智, 高橋 真, An. Subramanian, Touch Seang Tana
    第50回日本水環境学会年会 2016年03月
  • Structural preference of OH-PCBs to activate the Baikal Seal estrogen receptors  [通常講演]
    Yoshinouchi, Y, Hirano, M, Nomiyama, K, Tanabe, S, Kim, E. Y, Iwata, H
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Effects of prenatal exposure to BPA on the growth and organ development in postnatal rats  [通常講演]
    Yamamoto, K, Hoa, N. T, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Assessment of metabolic potential of polyhlorinated biphenyl congeners in the beagle dog liver by in vitro and in silico approaches  [通常講演]
    Yoo, J, Hirano, M, Nomiyama, K, Kim, E. Y, Tanabe, S, Iwata, H
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Hepatic transcriptome analysis to assess the effects of polychlorinated biphenyls on beagle dogs  [通常講演]
    Tamura, S, Yoo, J, Mizukawa, H, Agusa, T, Hirano, M, Eguchi A, Nomiyama, K, Tanabe, S, Kim, E. Y, Iwata, H
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Proteomic analysis for PCBs toxicity in the dog brain  [通常講演]
    Takaguchi, K, Nomiyama, K, Claret, L. M, Kusaki, M, Yoo, J, Mizukawa, H, Iwata, H, Kunisue, T, Tanabe, S
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Influence of lipid compositions on the brain distribution of PCBs and OH-PCBs in triped dolphins  [通常講演]
    Ochiai, M, Nomiyama, K, Isobe, T, Yamada, T. K, Tajima, Y, Amano, M, Iwata, H, Tanabe, S
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Toxicological assessment of PCBs and Hydroxy-metabolites (OH-PCBs) in the brain of dogs using metabolomics approach  [通常講演]
    Nomiyama, K, Eguchi, A, Mizukawa, H, Yoo, J, Takaguchi, K, Yamamoto, Y, Oshihoi, T, Iwata, H, Kunisue, T, Tanabe, S
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Effect of prenatal exposure of BPA on the transcriptome in chicken embryos  [通常講演]
    Itoh, S, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Transcriptome analysis to identify adverse outcome pathways mediated by the aryl hydrocarbon receptor in TCDD-treated red seabream embryos  [通常講演]
    Iida, M, Fujii, S, Uhida, M, Nakamura, H, Kagami, Y, Agusa, T, Hirano, M, Bak, S. M, Kim, E. Y, Iwata, H
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Ecological factors drive natural selection pressure affecting avian dioxin receptor genotypes  [通常講演]
    Hwang, J. H, Park, J. Y, Park, H. J, Bak, S. M, Hirano, M, Iwata, H, Park, Y. S, Kim, E. Y
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Liver transcriptome analysis to assess the effects of prenatal exposure to bisphenol a of rat offspring  [通常講演]
    Hoa, T. N, Yamamoto, K, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • Hirano, M., Uchida, M., Kusano, T., Arizono, K. and Iwata, H.  [通常講演]
    Effects of a naturally occurring dioxin, tribromodibenzo-p-dioxin on, the, mysid transcriptome
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers  [通常講演]
    Lauan, M. C, Yoo, J, Agusa, T, Hirano, M, Kim, E. Y, Iwata, H
    Assessment of effects of dioxins in the Baikal seal (Pusa Sibirica) by proteome and transcriptome analyses 2016年03月
  • Past, present, and future perspectives of environmental toxicology at Ehime University: advent of an era of the authentic animal study  [通常講演]
    Iwata, H
    International Symposium of Environmental Chemistry and toxicology - To Accelerate a Global Network of Environmental Researchers 2016年03月
  • OH-PCBsによるバイカルアザラシ エストロゲン受容体α・β転写活性化能の評価  [通常講演]
    芳之内結加, 平野将司, 野見山桂, 田辺信介, 金 恩英, 岩田久人
    環境ホルモン学会第18回研究発表会 2015年12月
  • イヌ脳中 PCBs, OH-PCBs の毒性影響評価:メタボロミクスアプローチ  [通常講演]
    野見山 桂, 江口哲史, 水川葉月, Jean Yoo, 高口倖暉, 山本泰央, 国末達也, 岩田久人, 田辺信介
    環境ホルモン学会第18回研究発表会 2015年12月
  • トランスクリプトーム解析によるPCBsを曝露したイヌへの影響評価  [通常講演]
    田村沙弥, 劉 珍, 水川葉月, 阿草哲郎, 平野将司, 江口哲史, 野見山 桂, 田辺信介, 金 恩英, 岩田久人
    ,環境ホルモン学会第18回研究発表会 2015年12月
  • In silico and in vitro screening of the effects of PPCPs on mysid ecdysteroid receptor signaling  [通常講演]
    Hirano, M, Ohno, Y, Iwata, H
    環境ホルモン学会第18回研究発表会 2015年12月
  • イヌ脳に及ぼす PCBs の影響:プロテオーム解析による評価  [通常講演]
    高口倖暉, 野見山 桂, Claret Lauan Maria, Jean Yoo, 水川葉月, 岩田久人, 国末達也, 田辺信介
    環境ホルモン学会第18回研究発表会 2015年12月
  • Effects of prenatal exposure to bisphenol A on the liver transcriptome of rat offspring  [通常講演]
    Hoa, N. T, Yamamoto, K, Agusa, T, Hirano, M, Ochiai, M, Kim, E. Y, Iwata, H
    環境ホルモン学会第18回研究発表会 2015年12月
  • Lipid composition in the brain compartments of striped dolphins (Stenella coeruleoalba) in relation to the accumulation of environmental pollutants (PCBs and OH-PCBs)  [通常講演]
    Ochiai, M, Nomiyama, K, Isobe, T, Yamada, T. K, Tajima, Y, Iwata, H, Amano, M, Tanabe, S
    21st Biennial Society for Marine Mammalogy Conference on the Biology of Marine Mammals 2015年12月
  • Toxicological assessment of polychlorinated biphenyls and their metabolites in the Baikal seal (Pusa sibirica)  [通常講演]
    Nomiyama, K, Hirakawa, S, Kanbara, C, Imaeda, D, Yoo, J, Kunisue, T, Kim, E. Y, Iwata, H, Tanabe, S
    Leading Symposium on Chemical Hazard and Adaptability in Animals – The Current Challenge of Young Researchers 2015年12月
  • Contamination by arsenic and other trace elements in groundwater from the Red and Mekong River Deltas  [通常講演]
    Agusa, T, Iwata, H, Kunito, T, Inoue, S, Kubota, R, Karri, R, Minh, T. B, Tue, N. M., Ha, N. N., Tu, N. P. C, Charaborty, P, Chamnan, C, Trang, P. T. K, Reungsang, A, Srisuk, K, Nakamura, S, Takizawa, S, Subramanian, A, Tuyen, B. C, Viet, P. H, Tana, T. S, Tanabe, S
    The Second Myanmar-Japan Symposium 2015年12月
  • Proteome and transcriptome analyses for identification of pathways affected by dioxin accumulation in Baikal seals  [通常講演]
    Lauan, M. C, Yoo,, J, Agusa, T, Hirano, M, Iwata, H
    42nd Philippine Society of Biochemistry and Molecular Biology Annual Convention 2015年12月
  • Toxicological assessment of polychlorinated biphenyls (PCBs) and hydroxylated PCBs (OH-PCBs) in the brain of dogs using metabolomics approach  [通常講演]
    Nomiyama, K, Eguchi, A, Mizukawa, H, Yoo, J, Takaguchi, K, Yamamoto, Y, Oshihoi, T, Iwata, H, Kunisue, T, Tanabe, S
    Society of Environmental Toxicology and Chemistry (SETAC) North America 36th Annual Meeting 2015年11月
  • Omics approach of proteomic and metabolomics analysis for PCBs toxicity in the dog brain  [通常講演]
    Takaguchi, K, Nomiyama, K, Lauan, M. C, Yoo, J, Mizukawa, H, Iwata, H, Kunisue, T, Tanabe, S
    Society of Environmental Toxicology and Chemistry (SETAC) North America 36th Annual Meeting 2015年11月
  • In vitro and in silico assessment of metabolic potential of PCB congeners by cytochrome P450 in the Baikal seal  [通常講演]
    Yoo. J, Hirano, M, Mizukawa, H, Nomiyama, K, Agusa, T, Kim, E. Y, Tanabe, S, Iwata, H
    The Korean Society of Environmental health and Toxicology 2015年10月
  • In vitro and in silico assessment of metabolic potential of polychlorinated biphenyls in the beagle dog  [通常講演]
    Yoo, J, Nomiyama, K, Kim, E. Y, Tanabe, S, Iwata, H
    The Korean Society of Environmental health and Toxicology 2015年10月
  • Persistent environmental pollutants in Asian coastal waters – contamination of dolphin brains  [通常講演]
    Ochiai, M, Nomiyama, K, Isobe, T, Yamada, T. K, Tajima, Y, Makara, M, Amano, M, Matsuishi, T, Iwata, H, Tanabe, S
    Asian Society of Conservation Medicine Meeting 2015年10月
  • バイカルアザラシ エストロゲン受容体を介したビスフェノール類によるアンタゴニスト作用の評価  [通常講演]
    芳之内結加, 清水沙千子, 李 鎮善, 平野将司, 鈴木賢一, 中田晴彦, 金 恩英, 岩田久人
    第24回環境化学討論会 2015年06月
  • ポリ塩化ビフェニル(PCBs)曝露によるイヌ異物代謝酵素シトクロムP450発現への影響評価  [通常講演]
    田村沙弥, 劉 珍, 水川葉月, 阿草哲郎, 平野将司, 野見山 桂, 田辺信介, 金 恩英, 岩田久人
    第24回環境化学討論会 2015年06月
  • ポリ塩化ビフェニル(PCBs)を曝露したイヌの脳プロテオーム解析による毒性影響評価  [通常講演]
    高口倖暉, 野見山 桂, Claret, Lauan Maria, 草木桃子, Jean Yoo, 水川葉月, 岩田久人, 国末達也, 田辺信介
    第24回環境化学討論会 2015年06月
  • メタボローム解析によるイヌ脳中PCBs, OH-PCBs の毒性影響評価  [通常講演]
    野見山桂, 江口哲史, 水川葉月, Jean Yoo, 高口倖暉, 山本泰央, 忍穂井 智子, 岩田久人, 国末達也, 田辺信介
    ,第24回環境化学討論会 2015年06月
  • Ecological factors affecting natural selection of avian AHR1 genotypes  [通常講演]
    Hwang J. H, Park, H. J, Bak, S. M, Hirnao, M, Iwata, H, Park, Y. S, Kim, E. Y
    18th International Symposium on Pollutant Responses in Marine Organisms 2015年05月
  • In vitro and in silico assessment of transactivation potencies of Baikal seal estrogen receptors  [通常講演]
    Yoshinouchi, Y, Shimizu, S, Lee, J. S, Hirano, M, Agusa, T, Suzuki, K. T, Nakata, H, Kim, E. Y, Iwata, H
    18th International Symposium on Pollutant Responses in Marine Organisms 2015年05月
  • Comparison of hepatic cytochrome P450-dependent metabolic potencies of polychlorinated biphenyls in the caniformia, the Baikal seal and the beagle dog  [通常講演]
    Yoo, J, Mizukawa, H, Nomiyama, K, Kim, E. Y, Tanabe, S, Iwata, H
    18th International Symposium on Pollutant Responses in Marine Organisms 2015年05月
  • Hepatic proteome analysis of Baikal seals contaminated with dioxis and related compounds  [通常講演]
    Lauan, M. C, Agusa, T, Hirano, M, Iwata, H, Kim, E. Y, Yoo, J
    18th International Symposium on Pollutant Responses in Marine Organisms 2015年05月
  • Identification of functional xenobiotic-responsive elements controlling AHR2 expression of red seabream (Pagrus major)  [通常講演]
    Bak, S. M, Iida, M, Soshilov, A. A, Denison, M. S, Iwata, H, Kim, E. Y
    18th International Symposium on Pollutant Responses in Marine Organisms 2015年05月
  • Hepatic cytochrome P450-dependent metabolic potency of polychlorinated biphenyls in the Baikal seal (Pusa sibirica)  [通常講演]
    Yoo, J, Hirano, M, Mizukawa, H, Nomiyama, K, Agusa, T, Kim, E. Y, Tanabe, S, Iwata, H
    18th International Symposium on Pollutant Responses in Marine Organisms 2015年05月
  • The autoinduction mechanism of aryl hydrocarbon receptor 2 (AhR2) through TCDD-activated AhR1/2 in the red seabream (Pusa major)  [通常講演]
    Bak, S, Kim, E. Y, Iida, M, Iwata, H
    Society of Toxicology (SOT) 54th Annual Meeting 2015年03月
  • Relationship between mRNA expression level and SNPs of AS3MT in residents from arsenic-contaminated areas in Vietnam  [通常講演]
    Agusa, T, Kunito, T, Tue, N. M, Lan, V. T, Minh, T. B, Trang, P. T, Fujihara, J, Takeshita, H, Takahashi, S, Viet, P. H, Tanabe, S, Iwata, H
    Society of Toxicology (SOT) 54th Annual Meeting 2015年03月
  • Strain-differences in the proteome of ioxin-sensitive and –resistant mice treated with 2,3,7,8-tetrabromodibenzo-p-dioxin  [通常講演]
    Nguyen, T, Lauan, M, Yoo, J, Iida, M, Agusa, T, Kim, E. Y, Miyazaki, T, Nose, M, Iwata, H
    Society of Toxicology (SOT) 54th Annual Meeting 2015年03月
  • RNA-Seq analysis of the mysid crustacean transcriptome treated with naturally occurring 1,3,7-tribromodibenzo-p-dioxin  [通常講演]
    Hirano, M, Uchida, M, Kusano, T, Arizono, K, Iwata, H
    Society of Toxicology (SOT) 54th Annual Meeting, San Diego 2015年03月
  • ウミガメ類におけるヒ素化合物の蓄積特性  [通常講演]
    阿草哲郎, 高木 梢, Todd, W. Miller, 久保田 領志, 阿南 弥寿美, 岩田久人, 田辺信介
    第20回ヒ素シンポジウム 2014年12月
  • バイカルアザラシ エストロゲン受容体α・β転写活性化能の評価:in vitro ・ in silico法によるリガンド作用機序の解明  [通常講演]
    芳之内 結加, 清水 沙千子, 李 鎮善, 平野将司, 阿草哲郎, 鈴木賢一, 中田晴彦, 金 恩英, 岩田久人
    環境ホルモン学会 第17回研究発表会 2014年12月
  • バイカルアザラシ (Pusa sibirica) における水酸化PCBsの毒性影響評価,環境ホルモン学会  [通常講演]
    野見山 桂, 平川周作, 江口哲史, 今枝大輔, Yoo Jean, 国末達也, 岩田久人, 田辺信介
    環境ホルモン学会 第17回研究発表会 2014年12月
  • ポリ塩化ビフェニル(PCBs)曝露によるイヌ異物代謝酵素シトクロムP450への影響  [通常講演]
    田村沙弥, Yoo Jean, 水川葉月, 阿草哲郎, 平野将司, 野見山 桂, 田辺信介, 金 恩英, 岩田久人
    環境ホルモン学会 第17回研究発表会 2014年12月
  • パスウェイ解析によるTCDD曝露したマダイ胚のトランスクリプトームへの影響評価  [通常講演]
    飯田 緑, 藤井 聡, 内田雅也, 中村 浩, 鏡 良弘, Bak Su-Min, 金 恩英, 岩田久人
    環境ホルモン学会 第17回研究発表会 2014年12月
  • Functional characterization of the clathrin as a novel regulator of ecdysone receptor signaling pathway  [通常講演]
    Hirano, M, Suzuki, K, Iwata, H
    環境ホルモン学会 第17回研究発表会 2014年12月
  • Effects of a naturally occurring dioxin, 1,3,7- tribromodibenzo-p-dioxin on the mysid transcriptome  [通常講演]
    Hirano, M, Uchida, M, Kusano, T, Arizono, K, Iwata, H
    環境ホルモン学会 第17回研究発表会 2014年12月
  • バイカルアザラシ エストロゲン受容体α・β転写活性化能の評価:種差とE2 誘導等価係数  [通常講演]
    芳之内 結加, 清水 沙千子, 李 鎮善, 平野将司, 阿草哲郎, 鈴木賢一, 中田晴彦, 金 恩英, 岩田久人
    環境ホルモン学会 第17回研究発表会 2014年12月
  • Toxicological assessment of polychlorinated biphenyls (PCBs) and their metabolites (OH-PCBs) in the liver of wild Baikal seals (Pusa sibirica)
    Nomiyama, K, Hirakawa, S, Eguchi, A, Kanbara, C, Imaeda, D, Yoo, J, Kunisue, T, Kim, E. Y, Iwata, H, Tanabe, S
    International Conference of Asian Environmental Chemistry 2014 (ICAEC2014) 2014年11月
  • Toxicological assessment of polychlorinated biphenyls (PCBs) and their metabolites (OH-PCBs) in the liver of wild Baikal seals (Pusa sibirica): Application of microarray and biochemical analysis  [通常講演]
    Nomiyama, K, Hirakawa, S, Eguchi, A, Kanbara, C, Imaeda, D, Yoo, J, Kunisue, T, Kim, E. Y, Iwata, H, Tanabe, S
    International Conference of Asian Environmental Chemistry 2014 (ICAEC2014) 2014年11月
  • Isoform specific induction of aryl hydrocarbon receptor by TCDD in the red seabream (Pagrus major)  [通常講演]
    Bak, S. M, Iida, M, Iwata, H, Kim, E. Y
    DIOXIN Madrid 2014/34th International Symposium on Halogenated Persistent Organic Pollutants 2014年09月
  • Effects of polychlorinated biphenyls on the expression of cytochrome P450s in beagle dogs  [通常講演]
    Tamura, S, Yoo, J, Nomiyama, K, Mizukawa, H, Tanabe, S, Agusa, T, Kim, E. Y, Hirano, M, Iwata, H
    DIOXIN Madrid 2014/34th International Symposium on Halogenated Persistent Organic Pollutants 2014年09月
  • In vitro and in silico assessment of transactivation potencies of Baikal seal estrogen receptors α and β by persistent organic pollutants and bisphenols  [通常講演]
    Yoshinouchi, Y, Shimizu, S, Suzuki, K, Lee, J. S, Nakata, H, Hirano, M, Kim, E. Y, Agusa, T, Iwata, H
    DIOXIN Madrid 2014/34th International Symposium on Halogenated Persistent Organic Pollutants 2014年09月
  • Ecological factors as pressure of natural selection of AhR genotypes in avian species  [通常講演]
    Hwang, J. H, Park, H. J, Park, J. Y, Bak, S. M, Park, Y. S, Hirano, M, Kim, E. Y, Iwata, H
    DIOXIN Madrid 2014/34th International Symposium on Halogenated Persistent Organic Pollutants 2014年09月
  • 海棲高等動物はどのように水銀を解毒しているのか?  [通常講演]
    阿草哲郎, 高木 梢, Todd W Miller, 久保田 領志, 阿南 弥寿美, 岩田久人, 田辺信介
    第33回生体と金属・化学物質に関する研究会(チョークトーク2014) 2014年08月
  • 海棲哺乳類の肝臓におけるHg結合タンパク質  [通常講演]
    阿草哲郎, 安木進也, 池本徳孝, 國頭 恭, 馬場徳寿, 田辺信介, 岩田久人
    第25回日本微量元素学会 2014年07月
  • ホッキョクグマのシトクロムP4501Aおよび2BによるPCBs代謝能力の評価  [通常講演]
    古池 幸, 平野将司, 鈴木賢一, Yoo Jean, 阿草哲郎, Thomas, J. Evans, Kurunthachalam Kannan, 岩田久人
    環境ホルモン学会 第16回研究発表会 2013年12月
  • Identification of aminio acid residues critical for ligand binding and transactivation in ecdysone receptor  [通常講演]
    Hirano, M, Ishibashi, H, Kim, E. Y, Arizono, K, Iwata, H
    環境ホルモン学会 第16回研究発表会 2013年12月
  • TCDD曝露したマダイ胚のトランスクリプトーム解析  [通常講演]
    飯田 緑, 藤井 聡, 内田雅也, 中村 浩, 鏡 良弘, Bak, Su-Min, Kim, Eun-Young, 島 康洋, 岩田久人
    環境ホルモン学会 第16回研究発表会 2013年12月
  • ilico解析による化学物質と核内受容体, シトクロムP450の相互作用の評価  [通常講演]
    岩田久人, 平野将司, Kim, Eun-Young
    環境ホルモン学会 第16回研究発表会 2013年12月
  • ベトナム人におけるAS3MT遺伝子の発現量とSNPsの関係  [通常講演]
    阿草哲郎, 國頭 恭, Nguyen, Minh, Tue, Vi, T. M. Lan, Tu, B, Minh, Pham, T. K. Trang, 藤原純子, 竹下治男, 高橋 真, Pham, H. Viet, 田辺信介, 岩田久人
    第19回ヒ素シンポジウム 2013年11月
  • 無尾両生類のメタモルフォーゼにおける肝臓代謝酵素群の変化  [通常講演]
    鈴木賢一, 中の三弥子, Daniel, R. Buchholz, 岩田久人, 柏木啓子, 山本 卓, 柏木昭彦
    NGS現場会, 第三回研究会 2013年09月
  • Proteomic analysis of liver microsomes in X. tropicalis  [通常講演]
    Suzuki, K. I, Nakano, M, Watabe, M, Fukuta, Y, Iwata, H
    The 12th Human Proteome Organisation World Congress 2013年09月
  • Homology modeling and ligand docking simulations of avian AhRs to decipher the interspecies differences in responses to dioxins  [通常講演]
    Hirano, M, Ishibashi, H, Kim, E. Y, Arizono, K, Iwata, H
    The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2013) 2013年08月
  • In vitro and in silico analyses to predict the effects of environmental chemicals through the mysid ecdysteroid receptor signaling pathway  [通常講演]
    Hirano, M, Ishibashi, H, Kim, E. Y, Arizono, K, Iwata, H
    The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2013) 2013年08月
  • Functional characterization of aryl hydrocarbon receptor from the polar bear (Ursus maritimus)  [通常講演]
    Hwang, J. H, Jeong, L. R, Kannan, K, Evans, T. J, Iwata, H, Kim, E. Y
    The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2013) 2013年08月
  • Polychlorinated biphenyls and their hydroxylated metabolites (OH-PCBs) in the Baikal seals and implication from a toxicogenomic approach  [通常講演]
    Nomiyama, K, Eguchi, A, Hirakawa, S, Kanbara, C, Imaeda, D, Kim, E. Y, Iwata, H, Tanabe, S
    The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2013) 2013年08月
  • Thyroid hormone-mediated effects of dioxins in wild Baikal seals (Pusa sibirica)  [通常講演]
    Iwata, H, Hirakawa, S, Eguchi, A, Imaeda, D, Kunisue, T, Kim, E. Y, Kannan, K, Petrov, E. A, Batoev, V. B, Tanabe, S
    The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2013) 2013年08月
  • Isoform-specific responses of aryl hydrocarbon receptor to dioxins in red seabream (Pagrus major)  [通常講演]
    Bak, S. M, Kim, E. Y, Iida, M, Iwata, H
    The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2013) 2013年08月
  • Effect of aryl hydrocarbon receptor variants and hnRNPA2/B1 on dioxin-induced cyp1a1 transactivation in MRL/lpr and C3H/lpr  [通常講演]
    Cho, S. W, Suzuki, K. I, Miura, Y, Watanabe, M, Miyazaki, T, Nose, M, Iwata, H, Kim, E. Y
    The 33rd International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN2013) 2013年08月
  • バイカルアザラシの微量元素蓄積とその応答遺伝子の探索  [通常講演]
    阿草哲郎, 平川周作, 渡邉 泉, 池本徳孝, 宇高真行, 金 恩英, Evgeny, A, Petrov Valeriy, B. Batoev, 田辺信介, 岩田久人
    第22回環境化学討論会 2013年07月
  • Identification of cytochrome P450 enzymes in phenobarbital-treated mouse liver microsomes using 2-DE and MALDI-TOF/TOF  [通常講演]
    Lauan, M. C, Suzuki, K, Agusa, T, Iwata H
    rd International Conference on Proteomics and Bioinformatics 2013年07月
  • 組換え近交系マウスを用いたヒ素感受性遺伝子座の同定  [通常講演]
    阿草哲郎, 小森浩章, 曽我美子, 宮崎龍彦, 能勢眞人, 森 士朗, 久保田領志, 田辺信介, 岩田久人
    第24回日本微量元素学会 2013年06月
  • Isoform-specific reponses of aryl hydrocarbon receptor to dioxins in red seabream (Pagrus major)  [通常講演]
    Bak, S. M, Kim, E. Y, Iida, M, Iwata, H
    The XIII international Congress of Toxicology 2013 2013年06月
  • Identification of quantitative trait loci (QTL) associated with inorganic arsenic metabolism using recombinant inbred strains of mice  [通常講演]
    Agusa, T, Komori, H, Soga, Y, Nose, M, Mori, S, Kubota, R, Tanabe, S, Iwata, H
    The XIII International Congress of Toxicology 2013 2013年06月
  • In silico analysis of avian AHRs to decipher the molecular basis for interspecies differences in responses to dioxins  [通常講演]
    Hirano, M, Bak, S. M, Iwata, H, Kim, E. Y
    The XIII International Congress of Toxicology 2013 2013年06月
  • In vitro approach to predict AHR-mediated CYP1A induction by dioxins in cormorant population  [通常講演]
    Iwata, H, Thuruthippallil, L. M, Kubota, A, Kim, E. Y
    The XIII International Congress of Toxicology 2013 2013年06月
  • Effects of aryl hydrocarbon receptor and transcriptional co-factor(s) on transactivation in MRL/lpr and C3H/lpr mouse strains  [通常講演]
    Cho, S. W, Kim, E. Y, Suzuki, K, Miura, Y, Iwata, H, Miyazaki, T, Nose, M
    The XIII International Congress of Toxicology 2013 2013年06月
  • Identification and functional characterization of a novel chicken aryl hydrocarbon receptor isoform, 2nd AHR1  [通常講演]
    Lee, J. S, Iwabuchi, K, Nomaru, K, Nagahama, N, Kim, E. Y, Iwata, H
    The XIII International Congress of Toxicology 2013 2013年06月
  • Effects of aryl hydrocarbon receptor genetic variants on dioxin-induced transactivation in MRL/lpr and C3H/lpr mouse strains  [通常講演]
    Cho, S. E, Miura, Y, Suzuki, K, Miyazaki, T, Nose, M, Iwata, H, Kim, E. Y
    SETAC North America 33rd Annual Meeting 2012年11月
  • Accumulation feature of trace elements in mass-stranded harbor seals (Phoca vitulina) in the North Sea coast in 2002  [通常講演]
    Agusa, T, Yasugi, S, Iida, A, Ikemoto, T, Anan, Y, Kuiken, T, Osterhaus, A. D. M. E, Tanabe, S, Iwata, H
    SETAC North America 33rd Annual Meeting 2012年11月
  • Species-and congener-specific transactivation potencies of red seabream AHR1 and AHR2 by dioxins  [通常講演]
    Bak, S. M, Iida, M, Iwata, H, Kim, E. Y
    SETAC North America 33rd Annual Meeting 2012年11月
  • In vitro transactivation of avian AHR1 and AHR2 by dioxins to assess the species-specific sensitivity and CYP1A induction in the population-level  [通常講演]
    Iwata, H, Lee, J. S, Thuruthippallil, L. M, Kim, E. Y
    SETAC North America 33rd Annual Meeting 2012年11月
  • Binding of perfluorochemicals to PPARα: toward establishing the linkage between the initiating event and its downstream signaling  [通常講演]
    Ishibashi, H, Hirano, M, Kim, E. Y, Iwata, H
    SETAC North America 33rd Annual Meeting 2012年11月
  • Development of ecotoxicological tools for the assessment of susceptibility and risk  [招待講演]
    Iwata, H
    SETAC Asia Pacific 2012 Meeting 2012年09月
  • 鳥類の環境毒性学:AHRシグナル伝達系の特徴とダイオキシン類のリスク評価  [招待講演]
    岩田久人, Thuruthippallil, L. M, 久保田彰, Kim, E. Y
    第39回日本毒性学会学術年会 2012年07月
  • インドおよびフィリピンのe-wasteリサイクル労働者における微量元素曝露の実態  [通常講演]
    阿草哲郎, 滝上英孝, 藤森 崇, 江口哲史, 戸次加奈江, 吉田 綾, 寺園 淳, Ballesteros Jr, F. C, Parthasaraty, P, 高橋 真, Subramanian, A, 岩田久人, 田辺信介
    第21回環境化学討論会 2012年07月
  • 環境化学物質による甲殻類脱皮ホルモン受容体を介した影響の評価:in vitro / in silico 解析の結果  [通常講演]
    平野将司, 石橋弘志, 金 恩英, 有薗幸司, 岩田久人
    第21回環境化学討論会 2012年07月
  • Molecular characterization of Xenopus cytochrome P450 family 1-4 for assessing the biological effects of environmental pollutants on amphibians  [通常講演]
    Suzuki, T. K, Iwata, H
    第21回環境化学討論会 2012年07月
  • 組換え近交系マウスを用いたダイオキシン感受性規定因子の探索  [通常講演]
    三浦良彰, 阿草哲郎, 渡辺倫夫, 鈴木賢一, Cho, S. E, Kim, E. Y, 宮崎龍彦, 能勢眞人, 岩田久人
    第21回環境化学討論会 2012年07月
  • ヒ素代謝, 排泄に関与する感受性遺伝子の探索  [通常講演]
    阿草哲郎, 小森浩章, 曽我美子, 能勢眞人, 森 士朗, 久保田領志, 田辺信介, 岩田久人
    第21回環境化学討論会 2012年07月
  • Morphological abnormalities and pathogenesis of the peripheral nerve in developing red sea bream embryos treated with TCDD  [通常講演]
    Iida, M, Kim, E. Y, Murakami, Y, Shima, Y, Iwata, H
    第21回環境化学討論会 2012年07月
  • In vitro and in silico analyses of the catalytic function of the Baikal seal (Pusa sibirica) CYP2 genes  [通常講演]
    Yoo, J, Hirano, M, Kubota, A, Kim、E. Y, Iwata, H
    第21回環境化学討論会 2012年07月
  • Estimation of transactivation potencies of red seabream AHR1/2 isogorms by dioxins  [通常講演]
    Bak, S. M, Iida, M, Iwata, H, Kim, E. Y
    第21回環境化学討論会 2012年07月
  • Molecular and functional characterization of 2nd AHR1 in the chicken (Gallus gallus)  [通常講演]
    Lee, J. S, Iwabuchi, K, Nomaru, K, Kim, E. Y, Iwata, H
    第21回環境化学討論会 2012年07月
  • Alternative approaches to wildlife testing for toxicological risk assessment: a case study on AHR-mediated CYP1A induction by dioxin and related compounds in the common cormorant (Phalacrocoraax carbo)  [通常講演]
    Thuruthippallil, L. M, Kim, E. Y, Kubota, A, Iwata, H
    第21回環境化学討論会 2012年07月
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced disruption of the peripheral nervous system of developing red seabream (Pagrus major) Embryos  [通常講演]
    Iida, M, Kim, E. Y, Murakami, Y, Shima, Y, Iwata, H
    The Society of Toxicology 51th Annual Meeting 2012年03月
  • In silico docking of polychlorinated biphenyls with cytochrome P450 2A, 2B, and 2C from the Baikal seal (Pusa sibirica)  [通常講演]
    Yoo, J, Hirano, M, Kim, E. Y, Iwata, H
    The Society of Toxicology (SOT) 51st Annual Meeting 2012年03月
  • Catalytic function of yeast-expressed Baikal seal CYP1A1, 1A2 and 1B1 proteins  [通常講演]
    Iwata, H, Yamaguchi, K, Kim, E. Y, Kubota, A
    The Society of Toxicology (SOT) 51th Annual Meeting 2012年03月
  • Transactivation potencies of common cormorant (Phalacrocorax carbo) aryl hydrocarbon receptor 1 and 2 isoforms by dioxins and related compounds  [通常講演]
    Thuruthippallil, L. M, Kim, E. Y, Iwata, H
    The Society of Toxicology 51th Annual Meeting 2012年03月
  • Screening of environmental pollutants as ligands of constitutive androstane receptor using surface plasmon resonance array system  [通常講演]
    Pham, T. D, Ishibashi, H, Kim, E. Y, Iwata, H
    The Society of Toxicology (SOT) 51th Annual Meeting 2012年03月
  • Gene loci associated with metabolism of inorganic arsenic in mice  [通常講演]
    Agusa, T, Komori, H, Soga, Y, Nose, M, Mori, S, Kubota, R, Tanabe, S, Iwata, H
    The Society of Toxicology (SOT) 51th Annual Meeting 2012年03月
  • Human exposure to trace elements from e-waste recycling sites in the Philippines  [通常講演]
    Agusa, T, Takigami, H, Eguchi, A, Fujimori, T, Bekki, K, Yoshida, A, Terazono, A, Ballesteros Jr, F. C, Takahashi, S, Iwata, H, Tanabe, S
    Workshop for Knowledge Sharing on E-waste in the Philippines (The 8th NIES Workshop on E-Waste) 2012年01月
  • バイカルアザラシ( Pusa sibirica )のエストロゲン受容体 (ERα, ERβ) の分子的特性と機能解析  [通常講演]
    清水沙千子, 鈴木賢一, 金恩英, 岩田久人
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • 組み換え近交系マウスにおけるダイオキシン感受性の系統差:AhR非依存的規定因子の探索  [通常講演]
    三浦良彰, 渡辺倫夫, 鈴木賢一, Cho, S. E, 金恩英, 宮崎龍彦, 能勢眞人, 岩田久人
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • Differential regulation of paralogous CYP1A6 and 1A7 genes in response to an ary hydrocarbon receptor agonist, 6-formylindolo[3,2-b] carbazole, in Xenopus laevis  [通常講演]
    Suzuki, K, Iwata, H
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • Functional characterization of red seabream Ah1/2 isoforms: comparison of transactivation potencies by dioxins  [通常講演]
    Bak, S. M, Iida, M, Iwata, H, Kim, E. Y
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • Transactivation potencies of common cormorant (Phalacrocorax carbo) aryl hydrocarbon receptor 1 and 2 isoforms by dioxins and related compounds  [通常講演]
    Thuruthippallil, L. M, Kim, E. Y, Iwata, H
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • In silico docking simulation of PCBs with the Baikal seal (Pusa sibirica) CYP2A, 2B, and 2C  [通常講演]
    Yoo, J, Hirano, M, Kim, E. Y, Iwata, H
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • TCDDによるマダイ胚の抹消神経系への影響  [通常講演]
    飯田緑, 金恩英, 村上安則, 島康洋, 岩田久人
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • Molecular and functional characterization of Baikal seal AHR-CYP1 signaling pathway  [通常講演]
    Iwata, H, Suda, T, Yamaguchi, K, Kim, E. Y
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • Direct binding affinities of perfluoroalkyl carboxylates and sulfonates to the Baikal Seal and human peroxisome proliferator-activated receptor α  [通常講演]
    Ishibashi, H, Kim, E. Y, Iwata, H
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • Measurement of direct binding of constitutive androstane recetor with persistent organic pollutants using a surface plasmon resonance array system  [通常講演]
    Pham, T. D, Ishibashi, H, Kim, E. Y, Iwata, H
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • In vitro and in silico analyses of the interaction of environmental chemicals with mysid ecdysteroid receptor  [通常講演]
    Hirano, M, Ishibashi, H, Kim E. Y, Arizono, K, Iwata, H
    環境ホルモン学会(日本内分泌攪乱化学物質学会)第14回研究発表会 2011年12月
  • Genetic susceptibility of arsenic metabolism  [招待講演]
    Agusa, T, Kunito, T, Lan, V. T. M, Fujiwara, J, Takeshita, H, Minh, T. B, Trang, P. T. K, Takahashi, S, Viet, P. H, Tanabe, S, Iwata, H
    BK21 Seminar 2011年12月
  • Transcriptional regulation of CYP1A genes in amphibians  [招待講演]
    Suzuki, K, Iwata, H
    BK21 Seminar 2011年12月
  • Hydrophobic ligand receptors and cytochrome P450s in animals: Biomarkers of chemical exposure, effects and sensitivity  [招待講演]
    Iwata, H
    BK21 Seminar 2011年12月
  • 組換え近交系マウスを用いたヒ素代謝感受性規定因子の探索  [通常講演]
    阿草哲郎, 小森浩章, 曽我美子, 能勢眞人, 森 士朗, 久保田領志, 田辺信介, 岩田久人
    第17回ヒ素シンポジウム 2011年11月
  • フィリピンのe-wasteリサイクル労働者における微量元素曝露の実態  [通常講演]
    阿草哲郎, 滝上英孝, 江口哲史, 藤森 崇, 戸次加奈江, 吉田 綾, 寺園 淳, Florencio C. Ballesteros Jr, 高橋 真, 岩田久人, 田辺信介
    第22回廃棄物資源循環学会研究発表会 2011年11月
  • Metallomics of wildlife: an approach to understand the mechanism of mercury detoxification  [通常講演]
    Agusa, T, Ikemoto, T, Kunito, T, Yasugi, S, Tanabe, S, Iwata, H
    SETAC (Society of Environmental Toxicology and Chemistry) North America 32nd Annual Meeting 2011年11月
  • Human exposure to trace elements from e-waste recycling sites in the Philippines  [通常講演]
    Agusa, T, Takigami, H, Eguchi, A, Fujimori, T, Bekki, K, Yoshida, A, Terazono, A, Ballesteros Jr., F.C, Takahashi, S, Iwata, H, Tanabe, S
    The Life Cycle of Metals: Improving Health, Environment and Human Security 2011年11月
  • Metabolism of As in residents from the areas with As-contaminated groundwater, Vietnam: effects of As exposure levels and genetic polymorphisms  [通常講演]
    Agusa, T, Kunito, T, Tue, N.M, Lan, V.T.M, Fujihara, J, Takeshita, H, Minh, T.B, Trang, P.T.K, Takahashi, S, Viet, P.H, Tanabe, S, Iwata, H
    IX International Society of Trace Element Research in Humans (ISTERH) 2011年10月
  • In vitro approaches for assessing the risk of toxic contaminants in wildlife  [通常講演]
    Iwata, H, Kim, E. Y
    4th International conference on environmental health science 2011年10月
  • Exposure, metabolism, and toxic effect of arsenic in residents from arsenic-contaminated groundwater areas of southeast asia  [通常講演]
    Agusa, T, Kunito, T, Inoue, S, Kubota, R, Ramu, K, Minh, T. B, Tue, N. M., Ha, N. N., Tu, N. P. C, Fujihara, J, Charaborty, P, Chamnan, C, Trang, P. T. K, Reungsang, A, Srisuk, K, Nakamura, S, Takizawa, S, Takeshita, H, Takahashi, S, Subramanian, A, Tuyen, B. C, Viet, P. H, Tana, T. S, Tanabe, S, Iwata, H
    lobal COE Program, International symposium on advanced studies by young scientists on environmental pollution and ecotoxicology 2011年08月
  • Quantitative analysis of the interaction of mammalian CARs with potential chemicals  [通常講演]
    Dau, P. T, Ishibashi, H, Kim, E. Y, Iwata, H
    Global COE Program, International symposium on advanced studies by young scientists on environmental pollution and ecotoxicology 2011年08月
  • TCDD exposure affects the peripheral nervous system in developing red seabreams (Pagrus major)  [通常講演]
    Iida, M, Kim, E. Y, Murakami, Y, Shima, Y, Iwata, H
    Global COE Program, International symposium on advanced studies by young scientists on environmental pollution and ecotoxicology 2011年08月
  • Potencies of CYP1A transactivation of cormorant AHR1 and AHR2 by dioxins and related compounds  [通常講演]
    Thuruthippallil, L. M, Kim, E. Y, Iwata, H
    Global COE Program, International symposium on advanced studies by young scientists on environmental pollution and ecotoxicology 2011年08月
  • Transcriptional regulation of CYP1A genes in amphibians, xenopus laevis and xenopus tropicalis  [通常講演]
    Suzuki, T. K, Iwata, H
    Global COE Program, International symposium on advanced studies by young scientists on environmental pollution and ecotoxicology 2011年08月
  • Molecular characterization and in silico analysis of cytochromep P450 2A, 2B, and 2C from the Baikal Seal (Pusa sibirica)  [通常講演]
    Yoo, J, Kim, E. Y, Iwata, H
    Global COE Program, International symposium on advanced studies by young scientists on environmental pollution and ecotoxicology 2011年08月
  • Catalytic function of in vitro expressed Baikal Seal CYP1A1, 1A2 and 1B1  [通常講演]
    Yamaguchi, K, Kim, E. Y, Kubota, A, Iwata, H
    Global COE Program, International symposium on advanced studies by young scientists on environmental pollution and ecotoxicology 2011年08月
  • In vitro and in silico analyses of the interaction of the mysid ecdysteroid receptor and environmental chemicals  [通常講演]
    Hirano, M, Ishibashi, H, Kim, E. Y, Arizono, K, Iwata, H
    Global COE Program, International symposium on advanced studies by young scientists on environmental pollution and ecotoxicology 2011年08月
  • ベトナム人におけるヒ素代謝能力とAS3MT遺伝子発現量の関係  [通常講演]
    阿草哲郎, 國頭 恭, Tue, N. M, Lan, V. T. M, Minh, T. B, Trang, P. T. K, 高橋 真, Viet, P. H, 田辺信介, 岩田久人
    第22回日本微量元素学会 2011年07月
  • Individual variations in arsenic metabolism in Vietnamese: the association with arsenic exposure and GSTP1 genetic polymorphisms  [通常講演]
    Agusa, T, Kunito, T, Tue, N. M, Lan, V. T. M, Fujihara, J, Takeshita, T, Minh, T. B, Trang, P. T. K, Takahashi, S, Viet, P. H, Tanabe, S, Iwata, H
    3rd International Symposium Metallomics 2011 2011年06月
  • Advanced alternative approaches to wildlife testing for toxicological research: A case study of the effects of perfluorochemicals on Baikal seals  [通常講演]
    Iwata, H, Ishibashi, H, Kim, E. Y
    The 4th Joint forum of environmental sciences 2011 2011年06月
  • Effects of environmental chemicals on DNA binding and transactivation of the crustacean ecdysteroid receptor  [通常講演]
    Hirano, M, Ishibashi, H, Kim, E. Y, Arizono, K, Iwata, H
    Pollutant Responses in Marine organisms 2011年05月
  • Molecular characterization of cytochrome P450 2A, 2B and 2C from the Baikal seal (Pusa sibirica)  [通常講演]
    Yoo, J, Kim, E. Y, Iwata, H
    Pollutant Responses in Marine Organisms 2011年05月
  • Development of the ligand screening method of baikal seal (Pusa sibirica) constitutive androstane receptor using a surface plasmon resonance biosensor array system  [通常講演]
    Dau, P. T, Ishibashi, H, Kim, E. Y, Iwata, H
    Pollutant Responses in Marine Organisms 2011年05月
  • Risk assessment of dioxins and related compounds in the black-footd albatross: Apprication on an in vitro approach  [通常講演]
    Thuruthippallil, L. M, Kim, E. Y, Iwata, H
    Pollutant Responses in Marine Organisms 2011年05月
  • Developmental effects of TCDD exposure on the peripheral nervous system in the red seabream (Pagrus major)  [通常講演]
    Iida, M, Kim, E. Y, Murakami, Y, Iwata, H
    Pollutant Responses in Marine Organisms 2011年05月
  • Functional characterization of in vitro expressed CYP1A1, 1A2 and 1B1 from the baikal seal (Pusa sibirica)  [通常講演]
    Yamaguchi, K, Kim, E. Y, Kubota, A, Iwata, H
    Pollutant Responses in Marine Organisms 2011年05月
  • Transactivation potencies of the baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α by perfluoroalkyl carboxylates and sulfonates: estimation of PFOA induction equivalency factors  [通常講演]
    Ishibashi, H, Kim, E. Y, Iwata, H
    Pollutant Responses in Marine Organisms 2011年05月
  • Cytochrome P450 CYP2 genes in the common cormorant: evolutionary relationships with diapsid CYP2 clan sequences and chemical effects on their expression  [通常講演]
    Kubota, A, Stegeman, J, Goldstone, J, Nelson, D, Kim, E. Y, Tanabe, S, Iwata, H
    10th International symposium on cytochrome P450 biodiversity and biotechnology 2010年10月
  • Transactivation potencies of Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α by perfluoroalkyl carboxylates and perfluoroalkyl sulfonates  [通常講演]
    Ishibashi, H, Kim, E. Y, Iwata, H
    10th International symposium on cytochrome P450 biodiversity and biotechnology 2010年10月
  • Regulation and catalytic function of avian CYP1A: Interspecies similarities and differences  [通常講演]
    Iwata, H, Kim, E. Y, Lee, J. S, Kubota, A
    10th International symposium on cytochrome P450 biodiversity and biotechnology 2010年10月
  • Risk assessment of dioxins and related compounds in the black-footed albatross: Application of an in vitro approach  [通常講演]
    Thuruthippallil L. M, Kim, E. Y, Iwata, H
    International symposium on modeling and analysis of marine environmental problems (MAMEP 2010) 2010年09月
  • Effects of endogenous and xenobiotic ligands on DNA binding and transactivation of the mysid ecdysteroid receptor  [通常講演]
    Hirano, M, Ishibashi, H, Kim, E. Y, Arizono, K, Iwata, H
    International symposium on modeling and analysis of marine environmental problems (MAMEP 2010) 2010年09月
  • Identification and characterization of CYP1 genes in Xenopus laevis and Xenopus tropicalis  [通常講演]
    Suzuki, K. T, Iwata, H
    International symposium on modeling and analysis of marine environmental problems (MAMEP 2010) 2010年09月
  • Transcriptional activities of Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α by perfluoroalkyl carboxylates and perfluoroalkyl sulfonates  [通常講演]
    Ishibashi, H, Kim, E. Y, Iwata, H
    International symposium on modeling and analysis of marine environmental problems (MAMEP 2010) 2010年09月
  • Accumulation of trace elements in harp seals (Phoca groenlandica) from Pangnirtung in Baffin Island, Canada  [通常講演]
    Agusa, T, Nomura, K, Kunito, T, Anan, Y, Iwata, H, Tanabe, S
    6th International Conference on Marine Pollution and Ecotoxicology 2010年06月
  • Methylation of inorganic arsenic and genetic polymorphisms in arsenic (+III oxidation state) methyltransferase in a Vietnamese population  [通常講演]
    Agusa, T, Fujihara, J, Takeshita, H, Tanabe, S, Iwata, H, Kunito, T, Minh, T. B, Trang, P. T. K, Viet, P. H
    The 3rd International Congress on Arsenic in the Environment 2010年05月
  • Arsenic, manganese and barium contamination in groundwater and human in Vietnam  [通常講演]
    Agusa, T, Inoue, S, Kunito, T, Minh, T. B., Tu, N. P. C, Ha, N. N, Kim Trang, P. T, Iwata, H, Tuyen, B. C, Viet, P. H, Tanabe, S
    The first international conference on environmental pollution, restoration and management [SETAC A/P Joint Conference] 2010年03月
  • 日本近海沿岸に漂着した鯨類に残留する 生物蓄積性有機ハロゲン化合物の網羅分析

MISC

  • 水川葉月, NGYUEN Hoa Thanh, 岩田久人, 野見山桂, 池中良徳, 中山翔太, 横山望, 市居修, 滝口満喜, KHIDKHAN Kraisiri, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.1C‐08 2019年06月
  • IN SILICO PREDICTION OF THE METABOLISM OF PCB CONGENERS BY CYTOCHROME P450 ISOZYMES IN YUSHO PATIENTS
    Hirakawa S, Miyawaki T, Hori T, Kajiwara J, Katsuki S, Hirano M, Yoshinouchi Y, Iwata H, Mitoma C, Furue M Organohalogen compounds 81 171 -174 2019年
  • 石橋 弘志, 平野 将司, 内田 雅也, 大倉 美咲, 石橋 康弘, 冨永 伸明, 岩田 久人, 有薗 幸司 環境ホルモン学会研究発表会要旨集 21回 39 -39 2018年12月
  • ゼブラフィッシュを用いたビスフェノールA代替物質の内分泌攪乱作用の評価
    久保田 彰, 李 宰承, 若山 裕己, 中村 倫子, 川合 佑典, 芳之内 結加, 岩田 久人, 平野 将司, 中田 晴彦 The Journal of Toxicological Sciences 43 (Suppl.) S269 -S269 2018年06月
  • 高口 倖暉, 中山 翔太, 池中 良徳, 石塚 真由美, 岩田 久人, 国末 達也, 田辺 信介, 野見山 桂, 西川 博之, 水川 葉月, 田上 瑠美, 草木 桃子, 横山 望, 市居 修, 滝口 満喜 日本毒性学会学術年会 45 (0) P -72 2018年 

    近年、ペット動物に対するポリ塩化ビフェニル(PCBs)および水酸化代謝物(OH-PCBs)の曝露による甲状腺ホルモン(THs)の恒常性への影響が注目されている。本研究ではPCBs曝露がペット動物のTHs恒常性に及ぼす影響を明らかにするため、イヌ・ネコのPCBs投与試験を実施し、PCBs曝露に伴う血清中THs濃度の変化を解析した。

    PCBs投与後から5日間、継続的に血清を採取し、THs濃度の変化を解析した結果、ネコ血清中THs濃度は、総THs、遊離型THsともに対照群と投与群の間に有意な変化は認められなかった。一方、イヌ血清中総THs濃度は投与群において、総L-サイロキシン(T4)と総3,5,3'-トリヨード-L-サイロニン(T3)の減少傾向がみられ、総PCBs濃度は総T4、総T3濃度と有意な負の相関を示した(p < 0.01)。一方、遊離型T4、遊離型T3濃度では、対照群と投与群の間に経時的な変化は認められなかったが、曝露後48、96時間目で有意に増加した(p < 0.05)。加えて、遊離型T4濃度は総OH-PCBs濃度と正の相関を示し(p < 0.01)、異性体別ではT4様構造の高塩素化OH-PCBsで同様の傾向が認められた。上記の結果および先行研究から、PCBs曝露によるイヌ血清中THsへの影響を推察した。PCBsがT4様構造のOH-PCBsへ代謝されてTHs輸送タンパクに競合結合し、結合できない遊離型T4が血中に増加することで、THsの臓器・組織への取り込み量が増加したと予測される。その結果、イヌ肝臓中のTHs濃度は増加し、PCBs曝露により肝臓中のAhR・CARが過剰に誘導されることで、UGTおよびSULTが誘導され、THsの抱合化を促進することで体外排泄量が増加し、血清中総T4、T3が減少したものと推察された。

  • ニワトリ胚における肝臓トランスクリプトームから予想されるtriclosanの有害性評価(Hazard assessment of triclosan predicted from the liver transcriptome in chicken embryos)
    Guo Jiahua, Ito Shohei, Nguyen Hoa Thanh, Yamamoto Kimika, Tanoue Rumi, Kunisue Tatsuya, Iwata Hisato 環境ホルモン学会研究発表会要旨集 20回 67 -67 2017年12月
  • 妊娠中にビスフェノールAに曝露したラットの肝臓トランスクリプトーム分析 それらの産仔のトランスクリプトームとの比較(Hepatic transcriptome profiles of rats exposed to bisphenol A during pregnancy: comparison with those oftheir offspring)
    Nguyen Hoa Thanh, Yamamoto Kimika, Iida Midori, Agusa Tetsuro, Hirano Masashi, Ochiai Mari, Kim Eun-Young, Iwata Hisato 環境ホルモン学会研究発表会要旨集 20回 74 -74 2017年12月
  • イヌ・アザラシ・マウスのエストロゲン受容体転写活性化能の種差を規定する分子機序
    芳之内 結加, 奥田 博貴, 平野 将司, 野見山 桂, 田辺 信介, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 20回 41 -41 2017年12月
  • ゼブラフィッシュをモデルとしたin silicoおよびin vivo解析によるビスフェノール類のエストロゲン様作用の評価
    久保田 彰, 若山 裕己, 中村 倫子, 川合 佑典, 芳之内 結加, 岩田 久人, 平野 将司, 中田 晴彦 環境ホルモン学会研究発表会要旨集 20回 65 -65 2017年12月
  • ビスフェノールAの出生前曝露によるニワトリ新生雛の肝臓トランスクリプトームへの影響の雌雄差
    伊藤 匠平, 飯田 緑, Nguyen Thanh Hoa, 阿草 哲郎, 平野 将司, 落合 真理, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 20回 68 -68 2017年12月
  • 高口倖暉, 野見山桂, 西川博之, 水川葉月, 田上瑠美, 芳之内結加, 横山望, 市居修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 岩田久人, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐02 2017年06月
  • 水酸化PCBsによるアザラシ・イヌエストロゲン受容体転写活性化能の評価
    芳之内 結加, 奥田 博貴, 平野 将司, 野見山 桂, 田辺 信介, 金 恩英, 岩田 久人 The Journal of Toxicological Sciences 42 (Suppl.) S236 -S236 2017年06月
  • ゼブラフィッシュをモデルとしたin vivoおよびin silico解析によるビスフェノール類のエストロゲン様作用の評価
    中村 倫子, 若山 裕己, 芳之内 結加, 森田 友里, 岩田 久人, 川合 佑典, 久保田 彰 The Journal of Toxicological Sciences 42 (Suppl.) S271 -S271 2017年06月
  • 有機リン系難燃剤およびその代謝物による発達期ゼブラフィッシュに対する影響
    森田 友里, 若山 裕己, 芳之内 結加, 岩田 久人, 川合 佑典, 久保田 彰 The Journal of Toxicological Sciences 42 (Suppl.) S271 -S271 2017年06月
  • Characteristics of PCB congeners accumulated in Yusho patients and estimation of their cytochrome P450-dependent metabolism by in silico docking simulation
    Hirakawa S, Miyawaki T, Hori T, Kajiwara J, Katsuki S, Hirano M, Yoshinouchi Y, Iwata H, Mitoma C, Furue M Organohalogen Compounds 79 28 -31 2017年
  • 日本のダイオキシン・AHR研究最前線 どこまで実態が解ったか? マダイにおけるアリル炭化水素受容体1(AHR1)およびAHR2によるAHR2遺伝子の自己誘導機構(Auto-induction mechanism of aryl hydrocarbon receptor 2(AHR2) gene by AHR1 and AHR2 in the red seabream)
    Bak Su-Min, Iida Midori, Soshilov Anatoly A, Denison Michael S, Iwata Hisato, Kim Eun-Young 環境ホルモン学会研究発表会要旨集 19回 37 -37 2016年12月
  • 日本のダイオキシン・AHR研究最前線 どこまで実態が解ったか? ダイオキシン感受性および遺伝子型関連環境因子を判別するための鳥類のアリル炭化水素受容体の構造特性(Structural characteristics of avian aryl hydrocarbon receptors to decipher dioxin susceptibility and ecological factors related to their genotypes)
    Hwang Ji-Hee, Park Hae-Jeong, Bak Su-Min, Hirano Masashi, Iwata Hisato, Park Jin-Young, Park Young-Suk, Kim Eun-Young 環境ホルモン学会研究発表会要旨集 19回 39 -39 2016年12月
  • ホッキョクグマ(Ursus maritimus)のアリル炭化水素受容体(AHR)の分子特性(Molecular characterization of aryl hydrocarbon receptor(AHR) in Polar bears(Ursus maritimus))
    Hwang Jihee, Kannan Kurunthachalam, Evans Thomas J, Iwata Hisato, Kim Eun-Young 環境ホルモン学会研究発表会要旨集 19回 83 -83 2016年12月
  • 鳥類のAHRと天然リガンドの相互作用のin silico/in vitro分析(In silico/in vitro analyses of the interaction of avian AHR and natural ligands)
    Koh Dong-Hee, Iwata Hisato, Kim Eun-Young 環境ホルモン学会研究発表会要旨集 19回 91 -91 2016年12月
  • 出生前のビスフェノールA曝露がラットの産仔の異なる生育段階での肝臓トランスクリプトームに及ぼす影響(Effects of prenatal exposure to bisphenol A on hepatic transcriptome at different life stages of rat offspring)
    Nguyen Thanh Hoa, Yamamoto Kimika, Agusa Tetsuro, Hirano Masashi, Ochiai Mari, Kim Eun-Young, Iwata Hisato 環境ホルモン学会研究発表会要旨集 19回 100 -100 2016年12月
  • PCBsのin vivo曝露によるビーグル犬の肝トランスクリプトームとメタボロームへの影響
    田村 沙弥, 阿草 哲郎, 平野 将司, 江口 哲史, 野見山 桂, 田辺 信介, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 19回 80 -80 2016年12月
  • ビスフェノールAの出生前曝露によるニワトリ新生雛の肝臓トランスクリプトームへの影響
    伊藤 匠平, 阿草 哲郎, 平野 将司, 落合 真理, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 19回 81 -81 2016年12月
  • ビスフェノールAの出生前曝露によるラット新生仔の体重・肝重量と肝遺伝子発現への影響
    山本 季美花, Nguyen Thanh Hoa, 阿草 哲郎, 平野 将司, 落合 真理, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 19回 96 -96 2016年12月
  • 山野俊介, GAMBOA Maribet, LAUAN Maria Claret, 岩田久人, 渡辺幸三 応用生態工学会研究発表会講演集 20th 73 2016年09月
  • 野見山桂, 高口倖暉, 江口哲史, 水川葉月, YOO Jean, 田村沙弥, 忍穂井智子, 岩田久人, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 25th ROMBUNNO.P‐030 2016年06月
  • 阿草哲郎, 江口哲史, TUE Nguyen Minh, LAN Vi Thi Mai, MINH Tu Binh, TRANG Pham Thi Kim, 高橋真, VIET Pham Hung, 田辺信介, 岩田久人 環境化学討論会要旨集(CD-ROM) 25th ROMBUNNO.2C‐01 2016年06月
  • 阿草哲郎, 岩田久人, 井上英, KARRI Ramu, NGUYEN Minh Tue, 田辺信介, 國頭恭, 久保田領志, MINH Tu Binh, TRANG Pham Thi Kim, VIET Pham Hung, NGUYEN Ngoc Ha, NGUYEN Phuc Cam Tu, TUYEN Bui Cach, CHARABORTY Paromita, CHAMNAN Chhoun, REUNGSANG Alissara, SRISUK Kriengsak, 中村哲, 滝沢智, 高橋真, ANNAMALAI Subramanian, Touch Seang Tana 日本水環境学会年会講演集 50th 258 2016年03月
  • 「薬毒同源」のヒ素化合物 環境化学物質および医薬品としての二面性 無機ヒ素の代謝に関与する遺伝子多型
    阿草 哲郎, 國頭 恭, Tue Nguyen Minh, Lan Vi Thi Mai, Minh Tu Binh, Trang Pham Thi Kim, 藤原 純子, 竹下 治男, 高橋 真, Viet Pham Hung, 田辺 信介, 岩田 久人 日本薬学会年会要旨集 136年会 (1) 226 -226 2016年03月
  • ラット産仔の肝臓トランスクリプトームに及ぼす出生前のビスフェノールAへの曝露の影響(Effects of prenatal exposure to bisphenol A on the liver transcriptome of rat offspring)
    Nguyen Thanh Hoa, Yamamoto Kimika, Agusa Tetsuro, Hirano Masashi, Ochiai Mari, Kim Eun-Young, Iwata Hisato 環境ホルモン学会研究発表会要旨集 18回 105 -105 2015年12月
  • アミecdysteroid受容体シグナル伝達に及ぼすPPCPsの影響についてのin silicoおよびin vitroスクリーニング(In silico and in vitro screening of the effects of PPCPs on mysid ecdysteroid receptor signaling)
    Hirano Masashi, Ohno Yuki, Iwata Hisato 環境ホルモン学会研究発表会要旨集 18回 110 -110 2015年12月
  • イヌ脳に及ぼすPCBsの影響 プロテオーム解析による評価
    高口 倖暉, 野見山 桂, Lauan Maria Claret, Yoo Jean, 水川 葉月, 岩田 久人, 国末 達也, 田辺 信介 環境ホルモン学会研究発表会要旨集 18回 106 -106 2015年12月
  • トランスクリプトーム解析によるPCBsを曝露したイヌへの影響評価
    田村 沙弥, 劉 珍, 水川 葉月, 阿草 哲郎, 平野 将司, 江口 哲史, 野見山 桂, 田辺 信介, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 18回 116 -116 2015年12月
  • イヌ脳中PCBs、OH-PCBsの毒性影響評価 メタボロミクスアプローチ
    野見山 桂, 江口 哲史, 水川 葉月, Yoo Jean, 高口 倖暉, 山本 泰央, 国末 達也, 岩田 久人, 田辺 信介 環境ホルモン学会研究発表会要旨集 18回 117 -117 2015年12月
  • OH-PCBsによるバイカルアザラシエストロゲン受容体α・β転写活性化能の評価
    芳之内 結加, 平野 将司, 野見山 桂, 田辺 信介, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 18回 142 -142 2015年12月
  • 山野俊介, GAMBOA Maribet, LAUAN Maria Claret, 岩田久人, 渡辺幸三 応用生態工学会研究発表会講演集 19th 99 2015年09月
  • 【環境発がんと衛生〜ヒ素研究の視点から〜】 Arsenic(+3 Oxidation State)Methyltransferase(AS3MT)遺伝子多型と無機ヒ素のメチル化能力との関連
    阿草 哲郎, 國頭 恭, Nguyen Minh Tue, Vi Thi Mai Lan, Tu Binh Minh, Pham Thi Kim Trang, 藤原 純子, 竹下 治男, 高橋 真, Pham Hung Viet, 田辺 信介, 岩田 久人 日本衛生学雑誌 70 (3) 186 -196 2015年09月 
    ヒ素代謝酵素の一塩基多型(SNP)を解析することにより、個人・集団レベルでヒ素代謝の変動、そしてヒ素の毒性影響を評価することができる。ヒトにおいて体内に取り込まれた無機ヒ素(IA)は代謝され、排泄される。その代謝経路については、主に2つの酵素が主要な役割を担っていると考えられる。その一つAS3MTはIAを2段階のステップを経てメチル化する。AS3MTのSNPとヒ素代謝との関連について、過去のin vivoおよび疫学的調査の報告とこれまでの研究結果についてまとめた。
  • ベトナム人のハプトグロビン(HP)多型解析とHP欠失アリルHPdelの地理的分布
    副島 美貴子, 神田 芳郎, 阿草 哲郎, 岩田 久人, 田辺 信介, 藤原 純子, 竹下 治男, 國頭 恭, Vi Thi Mai Lan, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, 高橋 真 DNA多型 23 (1) 108 -111 2015年07月 
    ベトナム人のハプトグロビン(HP)多型解析及びHP欠失アリルHPdelの地理的分布について検討した。試料はベトナ紅河デルタ地区の居住者293名の血液から抽出したゲノムDNAとし、TaqMan probe法に基づくHP2に特異的な配列とコントロール配列の比較C1法により、HP common多型とHPdelの同時検出を行った。サンプルを2AACT sampleの数値で分類した結果、HP型の遺伝子型は、-0.47〜0.37のHP2/HP2は144、0.64〜1.54のHP2/HP1は111、HP2のシグナルがないHP1/HP1は26、全てのシグナルを検出したHP2/HPdelは8、8HP5'とHPdelのシグナルはあるがHP2のシグナルがないHP1/HPdelは4であった。遺伝子型の頻度はハーディー・ワインバーグの平衡状態であり、HP1の頻度は近隣の東南アジア集団や過去のベトナム人解析の結果と類似していた。
  • 芳之内結加, 清水沙千子, LEE Jin‐Seon, 平野将司, 鈴木賢一, 中田晴彦, KIM Eun‐Young, KIM Eun‐Young, 岩田久人 環境化学討論会要旨集(CD-ROM) 24th ROMBUNNO.1A‐11 2015年06月
  • 野見山桂, 江口哲史, 水川葉月, YOO Jean, 高口倖暉, 山本泰央, 忍穂井智子, 岩田久人, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 24th ROMBUNNO.1A‐06 2015年06月
  • Species Differences in Xenobiotic/Drug Metabolism 異物/薬物代謝の種差解明の最先端 鳥類の化学物質感受性を規定する分子機序
    岩田 久人, 平野 将司, 金 恩英 The Journal of Toxicological Sciences 40 (Suppl.) S69 -S69 2015年06月
  • Soejima Mikiko, Agusa Tetsuro, Iwata Hisato, Fujihara Junko, Kunito Takashi, Takeshita Haruo, Vi Thi Mai Lan, Tu Binh Minh, Takahashi Shin, Pham Thi Kim Trang, Pham Hung Viet, Tanabe Shinsuke, Koda Yoshiro Legal Medicine 17 (1) 14 -16 2015年01月 
    ハプトグロビン(HP)遺伝子欠損対立遺伝子(HP del)は、無ハプトグロビン血症を引き起こし、輸血後の抗HP抗体産生によるアナフィラキシーの遺伝的危険因子である。この対立遺伝子の分布について、293名のベトナム人を対象にHP delの出現頻度を調査した。HP遺伝子型はリアルタイムPCRで決定した。HP1/HP1型が26名、HP1/HP2型が111名、HP1/HPdelが4名、HP2/HPdelが8名で、HPdelの出現頻度は0.020(12/586)であった。既に報告されているこの対立遺伝子の分布は、東アジア(モンゴル、日本、中国漢民族、韓国、台湾)と東南アジア(インドネシア、タイ)に限られている。中央アジア、南アジア、西アジア、ヨーロッパ、アフリカでは見つかっていない。この対立遺伝子は東アジアと東南アジアの祖先についての情報を得るためのマーカーになるかもしれない。
  • 天然のダイオキシンである1,3,7-tribromodibenzo-p-dioxinがmysid transcriptomeに及ぼす影響(Effects of a naturally occurring dioxin, 1,3,7-tribromodibenzo-p-dioxin on the mysid transcriptome)
    Hirano Masashi, Uchida Masaya, Kusano Teruhiko, Arizono Koji, Iwata Hisato 環境ホルモン学会研究発表会要旨集 17回 86 -86 2014年12月
  • Ecdyson受容体シグナル伝達経路の新規調節因子としてのclathrinの機能的特性(Functional characterization of the clathrin as a novel regulator of ecdysone receptor signaling pathway)
    Hirano Masashi, Suzuki Ken-ichi T, Iwata Hisato 環境ホルモン学会研究発表会要旨集 17回 87 -87 2014年12月
  • バイカルアザラシ エストロゲン受容体α・β転写活性化能の評価 種差とE2誘導等価係数
    芳之内 結加, 清水 沙千子, 李 鎭善, 平野 将司, 阿草 哲郎, 鈴木 賢一, 中田 晴彦, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 17回 53 -53 2014年12月
  • パスウェイ解析によるTCDD曝露したマダイ胚のトランスクリプトームへの影響評価
    飯田 緑, 藤井 聡, 内田 雅也, 中村 浩, 鏡 良弘, Bak Su-Min, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 17回 88 -88 2014年12月
  • ポリ塩化ビフェニル(PCBs)曝露によるイヌ異物代謝酵素シトクロムP450への影響
    田村 沙弥, Yoo Jean, 水川 葉月, 阿草 哲郎, 平野 将司, 野見山 桂, 田辺 信介, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 17回 106 -106 2014年12月
  • バイカルアザラシ(Pusa sibira)における水酸化PCBsの毒性影響評価
    野見山 桂, 平川 周作, 江口 哲史, 今枝 大輔, Yoo Jean, 国末 達也, 岩田 久人, 田辺 信介 環境ホルモン学会研究発表会要旨集 17回 107 -107 2014年12月
  • バイカルアザラシエストロゲン受容体α・β転写活性化能の評価 in vitro・in silico法によるリガンド作用機序の解明
    芳之内 結加, 清水 沙千子, 李 鎭善, 平野 将司, 阿草 哲郎, 鈴木 賢一, 中田 晴彦, 金 恩英, 岩田 久人 環境ホルモン学会研究発表会要旨集 17回 113 -113 2014年12月
  • 海棲哺乳類の肝臓におけるHg結合タンパク質
    阿草 哲郎, 安木 進也, 池本 徳孝, 國頭 恭, 馬場 徳寿, 田辺 信介, 岩田 久人 Biomedical Research on Trace Elements 25 (2) 66 -66 2014年06月
  • 環境発がんと衛生 ヒ素研究の視点から AS3MT遺伝子多型と無機ヒ素のメチル化能力との関係
    阿草 哲郎, 國頭 恭, Nguyen Minh Tue, Vi Thi Mai Lan, Tu Binh Minh, Pham Thi Kim Trang, 藤原 純子, 竹下 治男, 高橋 真, Pham Hung Viet, 田辺 信介, 岩田 久人 日本衛生学雑誌 69 (Suppl.) S167 -S167 2014年05月
  • Ecological factors as pressure of natural selection of AhR genotypes in avian species
    Hwang, J, Park, H.J, Bak, S.M, Hirano, M, Iwata, H, Park, J.Y, Park, Y.S, Kim, E.Y Organohalogen Compounds 76 725 -727 2014年
  • Ecdysone受容体のリガンド結合とトランス活性化に重要なアミノ酸残基の同定(Identification of amino acid residues critical for ligand binding and transactivation in ecdysone receptor)
    Hirano Masashi, Ishibashi Hiroshi, Kim Eun-Young, Arizono Koji, Iwata Hisato 環境ホルモン学会研究発表会要旨集 16回 119 -119 2013年12月
  • 分析技術の最近の進歩 In silico解析による化学物質と核内受容体・シトクロムP450の相互作用の評価
    岩田 久人, 平野 将司, Kim Eun-Young 環境ホルモン学会研究発表会要旨集 16回 31 -31 2013年12月
  • TCDD曝露したマダイ胚のトランスクリプトーム解析
    飯田 緑, 藤井 聡, 内田 雅也, 中村 浩, 鏡 良弘, Bak Su-Min, 金 恩英, 島 康洋, 岩田 久人 環境ホルモン学会研究発表会要旨集 16回 70 -70 2013年12月
  • ホッキョクグマのシトクロムP4501Aおよび2BによるPCBs代謝能力の評価
    古池 幸, 平野 将司, 鈴木 賢一, Jean Yoo, 阿草 哲郎, Evans Thomas J, Kannan Kurunthachalam, 岩田 久人 環境ホルモン学会研究発表会要旨集 16回 148 -148 2013年12月
  • 水川葉月, 野見山桂, 中津賞, 久保田彰, 石塚真由美, 岩田久人, 田辺信介 環境化学討論会要旨集(CD-ROM) 22nd ROMBUNNO.3-2D-7-3 2013年07月
  • 野見山桂, 江口哲史, 神原千佳, 今枝大輔, 平川周作, KIM Eun‐Young, 岩田久人, 田辺信介 環境化学討論会要旨集(CD-ROM) 22nd ROMBUNNO.3-2D-7-1 2013年07月
  • 組換え近交系マウスを用いたヒ素感受性遺伝子座の同定
    阿草 哲郎, 小森 浩章, 曽我 美子, 宮崎 龍彦, 能勢 眞人, 森 士朗, 久保田 領志, 田辺 信介, 岩田 久人 Biomedical Research on Trace Elements 24 (2) 103 -103 2013年06月
  • ダイオキシン様化学物質によるin vitroでの水鳥類AHR1とAHR2のトランス活性化能と野生集団のリスク評価への応用(In vitro transactivation potencies of cormorant AHR1 and AHR2 by dioxin-like chemicals and their application to risk assessment of the wild population)
    Iwata Hisato, Thuruthippalil Leena Mol, Kubota Akira, Kim Eun-Young 環境ホルモン学会研究発表会要旨集 15回 54 -54 2012年12月
  • 組換え近交系マウスにおけるダイオキシン感受性の系統差 AhR非依存的規定因子の探索(2)
    岩田 久人, 三浦 良彰, 阿草 哲郎, 能丸 幸治, 渡辺 倫夫, 鈴木 賢一, Cho See-Eun, Kim Eun-Young, 宮崎 龍彦, 能勢 眞人 環境ホルモン学会研究発表会要旨集 15回 140 -140 2012年12月
  • 三浦良彰, 阿草哲郎, 渡辺倫夫, 鈴木賢一, CHO See‐Eun, KIM Eun‐Young, 宮崎龍彦, 能勢眞人, 岩田久人 環境化学討論会要旨集(CD-ROM) 21st ROMBUNNO.3C-01 2012年07月
  • 阿草哲郎, 滝上英孝, 藤森崇, 江口哲史, 戸次加奈江, 吉田綾, 寺園淳, BALLESTEROS Florencio C.,Jr, BULBULE Keshav A, PARTHASARATY Peethmbaram, 高橋真, SUBRAMANIAN Annamalai, 岩田久人, 田辺信介 環境化学討論会要旨集(CD-ROM) 21st ROMBUNNO.P-012 2012年07月
  • 生態毒性試験生物の基礎研究 鳥類の環境毒性学 AHRシグナル伝達系の特徴とダイオキシン類のリスク評価
    岩田 久人, Lee Jin-Seon, Mol Thuruthippallil Leena, 久保田 彰, Kim Eun-Young The Journal of Toxicological Sciences 37 (Suppl.1) S37 -S37 2012年07月
  • ベトナム人の無機ヒ素メチル化能力とAS3MTのSNPsの関係
    阿草 哲郎, 國頭 恭, Nguyen Minh Tue, Vi Thi Mai Lan, Tu Binh Minh, Pham Thi Kim Trang, 藤原 純子, 竹下 治男, 高橋 真, Pham Hung Viet, 田辺 信介, 岩田 久人 Biomedical Research on Trace Elements 23 (2) 171 -171 2012年06月
  • Contamination by Trace Elements in E-waste Recycling Workers in the Philippines
    Agusa, T, Takigami, H, Eguchi, A, Fujimori, T, Bekki, K, Yoshida, A, Terazono, A, Ballesteros Jr, F. C, Takahashi, S, Iwata, H, Tanabe, S Workshop for Knowledge Sharing on E-waste in the Philippines (The 8th NIES Workshop on E-waste), Manila, Philippines 研究発表ペーパー・要旨(国際会議) 2012年01月
  • 清水沙千子, 鈴木賢一, KIM Eun‐Young, 岩田久人 日本内分泌かく乱化学物質学会研究発表会要旨集 14th 127 2011年12月
  • アミ類エクジステロイド受容体と環境化学物質の相互作用に関するin vitro・in silico分析(In vitro and in silico analyses of the interaction of environmental chemicals with the mysid ecdysteroid receptor)
    Hirano Masashi, Ishibashi Hiroshi, Kim Eun-Young, Arizono Koji, Iwata Hisato 環境ホルモン学会研究発表会要旨集 14回 46 -46 2011年12月
  • Surface plasmon resonance arrayシステムを用いた、アンドロスタン受容体と残留有機汚染物質の直接結合に関する調査(Measurement of direct binding of constitutive androstane receptor with persistent organic pollutants using a surface plasmon resonance array system)
    Pham Thi Dau, Ishibashi Hiroshi, Kim Eun-Young, Iwata Hisato 環境ホルモン学会研究発表会要旨集 14回 47 -47 2011年12月
  • Perfluoroalkyl carboxylatesとperfluoroalkyl sulfonatesの、バイカルアザラシとヒトのペルオキシソーム増殖因子活性化受容体αとの直接結合親和性(Direct binding affinities of perfluoroalkyl carboxylates and sulfonates to the Baikal seal and human peroxisome proliferator-activated receptor α)
    Ishibashi Hiroshi, Kim Eun-Young, Iwata Hisato 環境ホルモン学会研究発表会要旨集 14回 48 -48 2011年12月
  • Xenopus laevisにおける、アリール炭化水素受容体アゴニスト6-formylindolo[3,2-b]carbazoleに対するパラロガスなCYP1A6遺伝子とCYP1A7遺伝子の異なる調節(Differential regulation of paralogous CYP1A6 and 1A7 genes in response to an aryl hydrocarbon receptor agonist, 6-formylindolo[3,2-b]carbazole, in Xenopus
    Suzuki Ken-ichi T, Iwata Hisato 環境ホルモン学会研究発表会要旨集 14回 107 -107 2011年12月
  • 組み換え近交系マウスにおけるダイオキシン感受性の系統差 AhR非依存的規定因子の探索
    三浦 良彰, 渡辺 倫夫, 鈴木 賢一, Cho See-Eun, 金 恩英, 宮崎 龍彦, 能勢 眞人, 岩田 久人 環境ホルモン学会研究発表会要旨集 14回 116 -116 2011年12月
  • Human Exposure to Trace Elements from e-waste Recycling Sites in the Philippines
    Agusa T, Takigami H, Eguchi, A, Fujimori, T, Bekki, K, Yoshida, A, Terazono, A, Ballesteros Jr, F. C, Takahashi, S, Iwata, H, Tanabe, S The Life Cycle of Metals: Improving Health, Environment and Human Security, Tokyo, Japan; Proceedings vol.8 研究発表ペーパー・要旨(国際会議) 2011年11月
  • 野生生物のシトクロムP450と環境汚染物質
    岩田 久人 日本生化学会大会プログラム・講演要旨集 84回 4S3a -5 2011年09月
  • ベトナム人におけるヒ素代謝能力とAS3MT遺伝子発現量の関係
    阿草 哲郎, 國頭 恭, Nguyen Minh Tue, Vi Thi Mai Lan, Tu Binh Minh, Pham Thi Kim Trang, 高橋 真, Pham Hung Viet, 田辺 信介, 岩田 久人 Biomedical Research on Trace Elements 22 (2) 126 -126 2011年06月
  • 阿草哲郎, 滝上英孝, 江口哲史, 藤森崇, 戸次加奈江, 吉田綾, 寺園淳, BALLESTEROS Florencio C.,Jr, 高橋真, 岩田久人, 田辺信介 廃棄物資源循環学会研究発表会(CD-ROM) 22nd ROMBUNNO.E3-6 2011年
  • Fujihara Junko, Hasegawa Masanori, Kanai Rie, Agusa Tetsuro, Iwata Hisato, Tanabe Shinsuke, Yasuda Toshihiro, Yamaguchi Seiji, Takeshita Haruo Forensic Toxicology 29 (1) 65 -68 2011年01月 
    症例は三酸化ヒ素(ATO)療法を受けている4歳の急性前骨髄球性白血病(APL)女児で、その尿中および血清中のジメチルアルシン酸(DMA)、モノメチルアルソン酸(MMA)、As(V)、As(III)、および8-ヒドロキシ-2'-デオキシグアノシン(8-OHdG)の濃度を追跡した。これらのデータを論文に記載されている85歳のAPL患者の同様の分析データと比較すると、この女児のヒ素化合物の濃度とMMAおよびDMAの濃度(%)は高齢患者のそれらより低かった。一方、8-OHdGはDMAとのみ有意な正の相関性を示したが、他のヒ素化合物との間に相関性は見られなかった。本成績は論文記載の高齢APL患者のATO療法中の成績とは大きく異なるため、ヒ素中毒が懸念される場合には患者の年齢を考慮することが重要と思われる。本研究はATO療法を受けた小児APL患者の尿中の8-OHdGとヒ素化合物の濃度の関連性を示した最初の報告である。
  • 両生類におけるCYP1A転写調節(Transcriptional regulation of CYP1A genes in amphibians)
    Suzuki Ken-ichi T, Iwata Hisato 環境ホルモン学会研究発表会要旨集 13回 48 -48 2010年12月
  • 脊椎動物共通プライマーを用いた大規模ディファレンシャル・ディスプレイ法によるダイオキシン応答遺伝子の探索
    鵜飼 典佳, 遠藤 大二, 池田 晴喜, 伊藤 知子, 伊東 志野, 金 恩英, 岩田 久人, 北澤 多喜雄, 平賀 武夫, 寺岡 宏樹 日本獣医学会学術集会講演要旨集 150回 323 -323 2010年09月
  • 藤澤希望, 池中良徳, 山本秀明, KIM Eun‐Young, LEE Jin‐Seon, 岩田久人, 石塚真由美 北海道獣医師会雑誌 54 (8) 477 2010年08月
  • ベトナムのヒ素汚染地域住民におけるヒ素代謝に関与する要因
    阿草 哲郎, 岩田 久人, 藤原 純子, 國頭 恭, 竹下 治男, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, 田辺 信介 Biomedical Research on Trace Elements 21 (2) 137 -137 2010年06月
  • 阿草 哲郎, 藤原 純子, 竹下 治男, 田辺 信介, 岩田 久人, 國頭 恭, MINH Tu Binh, TRANG Pham Thi Kim, VIET Pham Hung 東洋出版DNA多型 18 242 -245 2010年05月 
    ベトナムのヒ素汚染地域(Thanh Vanh、Thach Hoa)の住民を対象に、3価ヒ素メチル転移酵素(AS3MT)のSNPとヒ素化合物の蓄積プロファイルの関係を解析した。井戸水と地域住民の尿および血液を採取した。地下水中総ヒ素濃度は<0.1〜145μg/lで、Thanh Vanhの濃度はThach Hoaよりも有意に高値を示した。また、Thanh Vanhのヒト尿中総ヒ素化合物および無機ヒ素、モノメチルアルソン酸(MMA)、ジメチルアルシン酸(DMA)の濃度は、Thach Hoaよりも有意に高かった。地下水中総ヒ素濃度とヒト尿中総ヒ素化合物、無機ヒ素、MMA、DMAの濃度の間には有意な正の相関関係を認めた。AS3MTの29ヶ所で変異を同定し、AS3MT 37616C>Aと37950C>Tは強い連鎖不平衡を示した。ベトナム人ではAS3MTの遺伝子多型がヒ素代謝に関与していると推測された。
  • 芳香族炭化水素受容体(AhR)の分子生物学的解析による鳥類のダイオキシン類感受性評価
    藤澤 希望, 池中 良徳, 山本 秀明, Kim Eun-Young, Lee Jin-Seon, 岩田 久人, 石塚 真由美 The Journal of Toxicological Sciences 35 (Suppl.) S132 -S132 2010年05月
  • エコトキシコゲノミクスへの応用を目的とした半網羅的ディファレンシャル・ディスプレイ法
    伊東 志野, 遠藤 大二, 池田 晴喜, 伊藤 知子, 鵜飼 典佳, 金 恩英, 岩田 久人, 北澤 多喜雄, 平賀 武夫, 寺岡 宏樹 The Journal of Toxicological Sciences 35 (Suppl.) S181 -S181 2010年05月
  • T. Agusa, J. Fujihara, H. Takeshita, S. Tanabe, H. Iwata, T. Kunito, T. B. Minh, P. T. K. Trang, P. H. Viet ARSENIC IN GEOSPHERE AND HUMAN DISEASES 329 -331 2010年
  • インド、ベトナム、カンボジア人の鉛汚染と影響評価について
    阿草 哲郎, 國頭 恭, Ramu Karri, Tu Binh Minh, Chamnan Chhoun, Pham Thi Kim Trang, Subramanian Annamalai, 岩田 久人, Pham Hung Viet, Touch Seang Tana, 田辺 信介 中毒研究 22 (2) 169 -170 2009年06月
  • ベトナム人におけるGSTスーパーファミリーの遺伝子多型と尿中ヒ素化合物プロファイルの関係
    阿草 哲郎, 岩田 久人, 藤原 純子, 國頭 恭, 竹下 治男, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet Biomedical Research on Trace Elements 20 (2) 163 -163 2009年06月
  • 藤原 純子, 阿草 哲郎, 竹下 治男, 副島 美貴子, 中島 たみ子, 岩田 久人, 田辺 信介 DNA多型 = DNA polymorphism 17 169 -172 2009年05月 
    今回著者等はベトナム人を対象に尿中ヒ素化合物とAS3MT遺伝子多型の関連について調査し、M287T多型と尿中無機ヒ素に占めるMMA vの割合とSNPsの関連について検討した。その結果、287M/287Tは287M/287Mと比較して尿中無機ヒ素化合物に占めるMMA vの割合が有意に高かった。このAS3MT M287T多型についての14集団比較では、M287T変異型の出現頻度は南アフリカのコーサ人で0.233と高く、他のアフリカ人及びコーカシア人でも類似した値を示した。一方、アジア人では中国人においては変異型が全く認められず、他のアジア人でも変異型出現率は0.04以下とコーカシア人やアフリカ人と比較して極めて低値を示した。他の17SNPsについて調査した10集団及び既報告との比較解析では、変異型の出現頻度に集団間での大きな差は認めなかった。
  • Fujihara Junko, Agusa Tetsuro, Tanaka Junko, Fujii Yoshimi, Moritani Tamami, Hasegawa Masanori, Iwata Hisato, Tanabe Shinsuke, Takeshita Haruo Forensic Toxicology 27 (1) 41 -44 2009年02月 
    三酸化砒素(ATO)は急性前骨髄球性白血病(APL)に対する効果的な治療薬である。ATO治療中の85歳の日本人男性のAPL患者について、尿中の8-OHdG濃度と砒素化合物(dimethylarsinic acid:DMA、monomethylarsonic acid:MMA、As:V、As:III)濃度を測定した。最初の地固め療法の間は特に8-OHdG、DMA、MMA濃度が上昇した。8-OHdGとDMAの濃度、8-OHdGとMMAの濃度、8-OHdGと全砒素化合物の濃度との間に正の有意な相関性が認められた。DMAとMMAが一緒に検出された時は、尿中の8-OHdGは砒素中毒のマーカーになり得ることが示された。
  • 酒井大樹, 岩田久人, KIM Eun‐Young, PETROV Evgeny A, 田辺信介 日本内分泌かく乱化学物質学会研究発表会要旨集 11th 45 2008年12月
  • ベトナム人におけるヒ素(+3酸化状態)メチルトランスフェラーゼ(AS3MT)の遺伝的多型と尿中ヒ素化合物の特徴との関連性(Relationship between Genetic Polymorphism of Arsenic (+3 oxidation state) Methyltransferase (AS3MT) and Profile of Urinary Arsenic Compounds in Vietnamese)
    Agusa Tetsuro, Fujihara Junko, Takeshita Haruo, Iwata Hisato, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, Tanabe Shinsuke Biomedical Research on Trace Elements 19 (3) 265 -267 2008年10月 
    AS3MTにおける287Met>Thrの遺伝的多型を調査し、これと尿中ヒ素の特徴との関連性について検討した。対象はベトナム紅河デルタの住民の尿試料100検体と血液試料100検体で、血液試料からはDNAを抽出して上記の多型を決定し、尿試料ではジメチルアルシン酸(DMA)、モノメチルアルソン酸(MMA)、亜ヒ酸塩(As III)、ヒ酸塩(As V)及びアルセノベタイン(AB)の濃度を測定した。その結果、この集団のアレル変異頻度は2%で、他のアジア人集団と類似していたが、白色人種やアフリカ人種よりは低かった。一方、尿中の主要ヒ素化合物は第1にDMA、次にABの順であったが、低レベルの無機ヒ素(IA)とMMAも検出した。TCヘテロ接合体の被験者の尿中MMA/IA濃度比はTTホモ接合体のそれより有意に高いことから、TC型被験者ではIAからMMAへのメチル化能力が高いと思われた。
  • Hisato Iwata, Hiroshi Ishibashi, Eun-Young Kim, Lin Tao, Kurunthachalam Kannan, Shinsuke Tanabe, Valeriy B. Batoev, Evgeny A. Petrov MARINE ENVIRONMENTAL RESEARCH 研究発表ペーパー・要旨(国際会議) 66 (1) 72 -73 2008年07月
  • ベトナム人におけるAS3MT遺伝子多型と尿中ヒ素化合物プロファイルの関係
    阿草 哲郎, 藤原 純子, 竹下 治男, 岩田 久人, Tu Binh Minh, Pham Thi Kim Trang, Pham Hung Viet, 田辺 信介 Biomedical Research on Trace Elements 19 (2) 196 -196 2008年06月
  • 藤原 純子, 竹下 治男, 阿草 哲郎, 岩田 久人, 安田 年博 DNA多型 = DNA polymorphism 16 175 -178 2008年05月 
    体内に取り込まれた無機ヒ素は還元とメチル化を繰り返し、Asv→AsIII→Methylarsonic acid(MMAv)→methylarsonous acid(MMAIII)→Dimethylarsinic acid(DMAv)→Dimethylarsinous acid(DMAIII)へと代謝される。ヒ素を含む地下水を飲用するベトナム人を対象にヒ素代謝に寄与する遺伝的多型部位を探索した。地下水中ヒ素が高濃度で、ヒ素汚染地域として知られるRed River Delta内のLiem ThuanとHoa Hau地区に住むベトナム人32家系100例を対象とした。全例でDMAvおよびMMAvが検出され、100試料中、98試料でAsIII、5試料でAsvを検出した。尿中のヒ素化合物に占めるDMAvの割合にばらつきがみられた。GSTO1 A140Dは毛髪中総ヒ素濃度において、A140/A140はA140/D140に比較して有意に高値であった。GSTM1 null typeは尿中DMAvの割合がactive typeに比較して有意に低かった。
  • Agusa Tetsuro, Takagi Kozue, Iwata Hisato, Tanabe Shinsuke Biomedical Research on Trace Elements 19 (1) 63 -66 2008年04月 
    タイマイとミドリガメにおける砒素の蓄積特性を検討するため、その総砒素化合物濃度と個別砒素化合物濃度を測定した。総砒素組織分布結果から、いずれの種においても筋肉内の濃度が最も高かった。タイマイの総砒素組織濃度はミドリガメより有意に高く、下等海洋動物と同程度であった。上記の両種における砒素の化学種別分析からは主要砒素化合物がアルセノベタインであることが分かり、両種の肝臓には比較的高濃度の非抽出性砒素が認められた。興味深いことに、タイマイでは高濃度のトリメチルアルシンオキシドが検出された。これらの両種の組織中のアルセノベタイン濃度は、それぞれの胃内容物より高かった。以上より、ウミガメはその餌からアルセノベタインを効率的に蓄積すると思われた。
  • Low induction potencies of cytochrome P450 2B and 3A by persistent organic pollutants in Baikal seal (Pusa sibirica)
    Sakai, H, Iwata, H, Kim, E-Y, Petrov, EA, Tanabe, S Interdisciplinary Studies on Environmental Chemistry-Biological Responses to Chemical Pollutants 研究発表ペーパー・要旨(全国大会,その他学術会議) 2008年03月
  • CONTAMINATION STATUS OF BROMINATED FLAME RETARDANTS (BFRS) IN BAIKAL SEALS (PUSA SIBIRICA)
    Isobe T, Ochi Y, Imaeda D, Sakai H, Hirakawa S, Tsydenova O, Amano M, Petrov E, Batoev V, Iwata H, Takahashi S, Tanabe S Organohalogen Compounds 70 1486 -1489 2008年
  • Residue levels, of OH-PCBs and PCBs in the blood of Baikal seals (Pusa Sibirica)
    Imaeda, D, Nomiyama, K, Kunisue, T, Iwata, H, Tsydenova, O, Takahashi, S, Amano, M, Petrov, E.A, Batoev, V.B, Tanabe, S Interdisciplinary Studies on Environmental Chemistry 速報,短報,研究ノート等(学術雑誌) 2 111 -117 2008年 [査読有り]
     
    Proceedings
  • タイマイとアオウミガメにおけるヒ素の蓄積特性
    阿草 哲郎, 高木 梢, 岩田 久人, 田辺 信介 Biomedical Research on Trace Elements 18 (2) 166 -166 2007年06月
  • Xenobiotic ligand profiles of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in Baikal seal (Pusa sibirica)
    Iwata, H, Sakai, H, Kadota, M, Kim, E-Y, Tanabe, S, Batoev, VB, Petrov, EA 14th International Symposium on Pollutant Responses In Marine Organisms (PRIMO) 研究発表ペーパー・要旨(全国大会,その他学術会議) 2007年05月
  • Agusa Tetsuro, Kubota Reiji, Kunito Takashi, Tu Binh Minh, Pham Thi Kim Trang, Chamnan Chhoun, Iwata Hisato, Pham Hung Viet, Touch Seang Tana, Tanabe Shinsuke Biomedical Research on Trace Elements 18 (1) 35 -47 2007年04月
  • Agusa Tetsuro, Kubota Reiji, Kunito Takashi, MINH Tu Binh, TRANG Pham Thi Kim, CHAMNAN Chhoun, IWATA Hisato, VIET Pham Hung, TANA Touch Seang, TANABE Shinsuke Biomedical research on trace elements 18 (1) 35 -47 2007年03月 
    Recently, As pollution was reported in groundwater from the Red River delta of Northern Vietnam and the Mekong delta of Southern Vietnam and Cambodia. Although the health of about 10 million people is at risk from the drinking tube well water, little information is available on the health effects of As exposure in the residents of these regions. Also, the countrywide survey on regional distribution of As pollution has not been conducted in these countries. At present, as far as we know, symptoms of chronic As exposure have not yet been reported, probably due to the relative short-term usage of the tube wells in the regions. However, oxidative DNA damage was observed in the residents of Cambodia and so further continuous usage of the tube well might cause severe damage to the health of the residents. In this article, we review literature concerning As pollution of groundwater and its health effects on residents in Vietnam and Cambodia. The mechanisms of As release to the groundwater is also discussed.
  • 栄養と化学物質と健康の接点 水圏生態系の化学物質汚染
    岩田 久人, 金 恩英, 山内 正信, 井上 英, 阿草 哲郎, 田辺 信介 薬学雑誌 127 (3) 417 -428 2007年03月
  • GENE EXPRESSION PROFILE IN THE LIVER OF BAIKAL SEALS (PUSA SIBIRICA): ASSOCIATION WITH DIOXINS AND RELATED COMPOUNDS
    Hirakawa S, Imaeda D, Nakayama K, Kim EY, Kunisue T, Tanabe S, Petrov EA, Batoev VB, Iwata H Organohalogen Compounds 69 1741 -1744 2007年
  • Agusa Tetsuro, Kunito Takashi, Ramu Karri, CHAMNAN Chhoun, TRANG Pham Thi Kim, MINH Tu Binh, SUBRAMANIAN Annamalai, IWATA Hisato, VIET Pham Hung, TANA Touch Seang, TANABE Shinsuke Biomedical research on trace elements 17 (4) 413 -416 2006年12月 
    In the present study, lead concentrations were determined in human blood collected from cities, dumping sites and reference sites in South India, North Vietnam and Cambodia. To evaluate human health effect of lead exposure, the &delta;-aminolevulinic acid dehydratase (ALAD) activities were also measured. Concentrations of lead in human blood ranged from 2.33 <I>&mu;</I>g/dl to 27.4 <I>&mu;</I>g/dl. Especially, concentrations in blood of residents from Perungudi (waste dumping site) and Palaverkadu (farming village) in South India were higher than those from other regions or those reported previously. Concentrations of lead in blood of some residents exceeded the threshold levels which can induce hypertension in adult and inhibit development of intelligence in fetus. Furthermore, significant negative correlations between blood lead levels and ALAD activities were observed in the residents from all the three countries, indicating possible suppression of that heme biosynthesis by lead in these residents.
  • Agusa Tetsuro, Kunito Takashi, Ramu Karri, Chamnan Chhoun, Pham Thi Kim Trang, Tu Binh Minh, Subramanian Annamalai, Iwata Hisato, Pham Hung Viet, Touch Seang Tana, Tanabe Shinsuke Biomedical Research on Trace Elements 17 (4) 413 -416 2006年12月 
    インド、ベトナム、カンボジアの都市部、ゴミ捨て場近隣及び漁村や農村等の地域より収集したヒト血液試料を対象に血中鉛濃度を測定した。また、鉛によるヒト健康への影響を評価するため、アミノレブリン酸デヒドラターゼ(ALAD)活性を測定した。その結果、ヒト血中の鉛濃度は、2.33μg/dL〜27.4μg/dlであった。特に、南インドにあるゴミ捨て場近隣のPerungudiと、漁村のPalaverkaduの住民で、血中鉛濃度が高かった。閾値を超える血中鉛濃度は、成人における高血圧や胎児における知的発達障害を引き起こすと考えられる。更に、全ての国で、血中鉛濃度とALAD活性の有意な負の相関が認められた。鉛により、ALADの血中合成が抑制されている可能性がある。
  • 小川真佐子, 松田知成, 松井三郎, 岩田久人, KIM Eun‐Yong, 田辺信介 日本内分泌かく乱化学物質学会研究発表会要旨集 9th 152 2006年11月
  • Constitutive androstane/ active receptor in Baikal seal: The transactivation potential of environmental pollutants as a sensing biomarker.
    Sakai, H, Iwata, H, Kim, E-Y, Miyazaki, N, Petrov, EA, Tanabe, S International Symposium 2006: Pioneering Study of Young Scientists on Chemical Pollution and Environmental Changes 研究発表ペーパー・要旨(全国大会,その他学術会議) 2006年11月
  • Satoko Niimi, Hisato Iwata, Mai Imoto, Michio X. Watanabe, Tatusya Kunisue, Eun-Young Kim, Kei Nakayama, Genta Yasunaga, Yoshihiro Fujise, Shinsuke Tanabe ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 研究発表ペーパー・要旨(国際会議) 232 674 -674 2006年09月
  • Michio X. Watanabe, Tatusya Kunisue, Hisato Iwata, Annamalai Subramanian, Shinsuke Tanabe ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 研究発表ペーパー・要旨(国際会議) 232 672 -672 2006年09月
  • 阿草 哲郎, 國頭 恭, RAMU Karri, CHARABORTY Paromita, CHAMNAN Chhoun, TRANG Pham Thi Kim, MINH Tu Binh, SUBRAMANIAN Annamalai, 岩田 久人, VIET Pham Hung, TANA Touch Seang, 田辺 信介 Biomedical research on trace elements 17 (2) 169 -169 2006年07月
  • Interspecies difference in ligand profiles of constitutive androstane receptor (CAR) in mouse and an aquatic mammal, Baikal seal (Pusa sibirica).
    Sakai, H, Iwata, H, Kim, E-Y, Miyazaki, N, Petrov, EA, Tanabe, S 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress 研究発表ペーパー・要旨(全国大会,その他学術会議) 2006年06月
  • 栄養と化学物質と健康の接点 水圏生態系の化学物質汚染
    岩田 久人, 田辺 信介 日本薬学会年会要旨集 126年会 (1) 117 -117 2006年03月
  • Tomoko Yasui, Eun-Young Kim, Hisato Iwata, Diana G. Franks, Sibel I. Karchner, Mark E. Hahn, Shinsuke Tanabe MARINE ENVIRONMENTAL RESEARCH 研究発表ペーパー・要旨(国際会議) 62 S70 -S71 2006年
  • Dong-Ha Nam, Eun-Young Kim, Hisato Iwata, Shinsuke Tanabe MARINE ENVIRONMENTAL RESEARCH 研究発表ペーパー・要旨(国際会議) 62 S88 -S89 2006年
  • Akira Kubota, Hisato Iwata, Eun-Young Kim, Shinsuke Tanabe, Kumiko Yoneda MARINE ENVIRONMENTAL RESEARCH 研究発表ペーパー・要旨(国際会議) 62 S43 -S44 2006年
  • Hisato Iwata, Yusuke Hirai, Satoko Baba, Eun-Young Kim, Shinsuke Tanabe MARINE ENVIRONMENTAL RESEARCH 研究発表ペーパー・要旨(国際会議) 62 S173 -S174 2006年
  • Masanobu Yamauchi, Eun-Young Kim, Hisato Iwata, Yasuhiro Shima, Shinsuke Tanabe MARINE ENVIRONMENTAL RESEARCH 研究発表ペーパー・要旨(国際会議) 62 S42 -S42 2006年
  • Akira Kubota, Hisato Iwata, Eun-Young Kim, Shinsuke Tanabe, Kumiko Yoneda MARINE ENVIRONMENTAL RESEARCH 研究発表ペーパー・要旨(国際会議) 62 S175 -S175 2006年
  • Eun-Young Kim, Tomohiro Sakamoto, Hisato Iwata, Shinsuke Tanabe, Nobuyuki Miyazaki, Evgeny A. Petrov MARINE ENVIRONMENTAL RESEARCH 研究発表ペーパー・要旨(国際会議) 62 S174 -S175 2006年
  • Agusa Tetsuro, Inoue Suguru, Kunito Takashi, KUBOTA Reiji, MINH Tu Binh, TRANG Pham Thi Kim, SUBRAMANIAN Annamalai, IWATA Hisato, VIET Pham Hung, TANABE Shinsuke Biomedical research on trace elements 16 (4) 296 -298 2005年12月
  • Agusa Tetsuro, Inoue Suguru, Kunito Takashi, Kubota Reiji, Tu Binh Minh, Pham Thi Kim Trang, Subramanian Annamalai, Iwata Hisato, Pham Hung Viet, Tanabe Shinsuke Biomedical Research on Trace Elements 16 (4) 296 -298 2005年12月 
    ベトナムのレッドリバーデルタにある二つの地域(Ha Nam省,Ha Tay省)の地下水中のヒ素汚染の分布を調査した.これらの両地域の数ヶ所から収集した地下水中のヒ素濃度は3.0〜486μg/lであり,殆どの地域でWHO飲料水ガイドラインの基準値(10μg/l)を超えていた.この結果から,両省の住民に対する健康リスクが憂慮され,ヒ素汚染はレッドリバーデルタ全体に及んでいると思われる.これら両地域の住民の尿中には,無機ヒ素化合物と共にモノメチルアルソン酸やジメチルアルシン酸(DMA)などのメチル化体が検出された.地下水中のヒ素濃度は住民の尿中の無機ヒ素化合物やDMAの濃度に関連しているため,住民は地域の地下水摂取を通してヒ素汚染に曝されていると考えられた
  • 【動物と環境毒物】 ダイオキシン曝露によるマダイ胚発生への毒性影響 形態異常の分子メカニズムの解明を目指して
    岩田 久人, 山内 正信, 金 恩英, 田辺 信介 中毒研究 18 (4) 333 -347 2005年10月
  • インド都市ゴミ集積場で捕獲したブタのダイオキシン類汚染と肝チトクロームP450への影響
    渡辺 倫夫, 國末 達也, 岩田 久人, Subramanian Annamalai, 田辺 信介 環境ホルモン学会研究発表会要旨集 8回 182 -182 2005年09月
  • 上田 浩三, 岩本 智史, 梅村 省三, 長屋 喜一, 岩田 久人, 田辺 信介 環境化学 : journal of environmental chemistry 15 (2) 311 -320 2005年06月 
    老朽化した都市ごみ焼却炉の解体工事に伴い, ダイオキシン類汚染土壌を現地で無害化処理した。無害化処理には移動型の間接加熱型キルンを用い, 排ガス処理には集じんスクラバーとHEPAフィルター, 活性炭フィルターを使用した。集じんスクラバーの凝縮水は, 平膜ろ過装置を用いて処理した。その結果, 土壌中ダイオキシン類濃度を平均3, 900pg-TEQ/9から37pg-TEQ/gまで低減 (分解率99%以上) させることに成功した。処理土壌の異性体組成を調べたところ, どの異性体も一様に土壌から除去されており, 処理した土壌においては脱塩素化による毒性換算値の増加は認められなかった。一方, 集じんスクラバー排水中のダイオキシン類は低塩素化体の比率上昇が認められた。排水に移行したダイオキシン類量は全体収支の約0.13%であり, 土壌から脱離しただけではなく, 無害化が確認できた。排気についても基準値を下回り, 本システムはダイオキシン類汚染土壌の無害化処理に有用であると結論された。
  • ダイオキシン暴露によるマダイ胚発生への毒性影響:形態異常の分子メカニズムの解明を目指して
    中毒研究 18 (4) 333 -347 2005年
  • 酒井大樹, 岩田久人, KIM Eun‐Young, 田辺信介, 宮崎信之, PETROV Evgeny A 日本内分泌かく乱化学物質学会研究発表会要旨集 7th 98 2004年12月
  • Agusa Tetsuro, Kunito Takashi, Fujihara Junko, Kubota Reiji, Minh Tu Binh, Pham Thi Kim Trang, Subramanian Annamalai, Iwata Hisato, Pham Hung Viet, Tanabe Shinsuke Biomedical Research on Trace Elements 15 (4) 339 -341 2004年12月
  • マイクロアレイを用いたカワウにおける潜在的毒性影響の評価 肝臓中の遺伝子発現プロファイルと化学物質蓄積レベルとの関係
    仲山 慶, 岩田 久人, 金 恩英, 久保田 彰, 田代 康介, 田辺 信介 環境ホルモン学会研究発表会要旨集 7回 107 -107 2004年12月
  • ベトナムのダンピングサイト周辺住人におけるダイオキシン類暴露 母乳中残留濃度と内分泌系への影響
    村岡 正義, 国末 達也, 岩田 久人, Minh Tu Binh, Minh Nguyen Hung, Tuyen Bui Cach, 田辺 信介 環境ホルモン学会研究発表会要旨集 7回 375 -375 2004年12月
  • H Iwata, EY Kim, S Tanabe DRUG METABOLISM REVIEWS 研究発表ペーパー・要旨(国際会議) 36 24 -24 2004年08月
  • ベトナム・ハノイ市における地下水の微量元素汚染とその飲用によるヒトへの曝露
    阿草 哲郎, 國頭 恭, 藤原 純子, 久保田 領志, Tu Binh Minh, Pham Thi Kim Trang, Subramanian Annamalai, 岩田 久人, Pham Hung Viet, 田辺 信介 Biomedical Research on Trace Elements 15 (2) 180 -180 2004年06月
  • Cloning and expression analysis of constitutive androstane receptor cDNAs in Baikal seal (Pusa sibirica) and northern fur seal (Callorhinus ursinus).
    Sakai, H, Iwata, H, Kim, E-Y, Tanabe, S, Miyazaki, N, Baba, N 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances 研究発表ペーパー・要旨(全国大会,その他学術会議) 2004年03月
  • Isolation of CYP1A1 cDNA and its mRNA expression related to TEQ level in Baikal seal (Pusa sibirica)
    Hirakawa S, Iwata H, Kim EY, Tanabe S, Miyazaki N Proceedings of 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances 208 -212 2004年
  • Effects of PCDDs/DFs/Co-PCB on hepatic protein expression profile in common cormorant population
    Proceedings of COE 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances 223 -227 2004年
  • Monitoring of gene expression profiles related to chemical contamination in common cormorant (Phalacrocorax carbo) liver with an oligo array
    Proceedings of COE 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances 218 -222 2004年
  • 平川 周作, 岩田 久人, 金 恩英, 田辺 信介, 宮崎 信之 環境毒性学会誌 7 (2) 55 -59 2004年
  • Influence of endocrine disruptors on reproduction of aquatic animals in Indochina
    Proceeding of "Internatinal Symposium on the Development Water Resource Management System in Mekong Watershed Hanoi, Vietnam, December 2004" 32 -40 2004年
  • Effects of PCDDs/DFs/Co-PCB on hepatic protein expression profile in common cormorant population
    Proceedings of COE 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances 223 -227 2004年
  • Monitoring of gene expression profiles related to chemical contamination in common cormorant (Phalacrocorax carbo) liver with an oligo array
    Proceedings of COE 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances 218 -222 2004年
  • Influence of endocrine disruptors on reproduction of aquatic animals in Indochina
    Proceeding of "Internatinal Symposium on the Development Water Resource Management System in Mekong Watershed Hanoi, Vietnam, December 2004" 32 -40 2004年
  • 馬場智子, 岩田久人, 酒井大樹, KIM E‐Y, 田辺信介 日本内分泌かく乱化学物質学会研究発表会要旨集 6th 287 2003年12月
  • カンボジアおよびベトナムにおける地下水のヒ素汚染とヒトへの影響
    久保田 領志, 金 恩英, 國頭 恭, Minh Tu Binh, 岩田 久人, 田辺 信介, Monirith In, Tana Touch Seang, Trang Pham, Thi Kim, Viet Pham Hung 環境ホルモン学会研究発表会要旨集 6回 95 -95 2003年12月
  • 環境と生体のインターフェイスとしての薬物代謝酵素と関連タンパク質の意義を考える 内分泌撹乱物質のリスク評価における水鳥と哺乳類の核受容体-CYPシクナリング経路(Importance of drug-metabolizing enzymes and relating proteins as the interface between organisms and environments: Nuclear Receptor-CYP Signaling Pathways in Aquatic Birds an
    Iwata Hisato, Kim Eun-Young, Tanabe Shinsuke 生化学 75 (8) 770 -770 2003年08月
  • ウミガメ類におけるメタロチオネイン異性体(MT-A,-B,-C)の存在とその組織分布
    阿南 弥寿美, 金 恩英, 國頭 恭, 岩田 久人, 田辺 信介 Biomedical Research on Trace Elements 14 (2) 149 -149 2003年06月
  • 東京産ハシブトガラスのダイオキシン類汚染と肝チトクローム P-450 系への影響
    平成14年度野生生物のダイオキシン類蓄積状況及び影響調査報告書 71 -94 2003年
  • カワウのダイオキシン類汚染と肝チトクロームP-450 系への影響
    平成14年度野生生物のダイオキシン類蓄積状況及び影響調査報告書 29 -67 2003年
  • 環境データの解析と環境中生物影響評価―生体汚染の実態解明とその影響評価に関する研究
    環境省環境技術開発等推進事業研究平成14年度報告書「環境中複合化学物質による次世代影響リスクの評価と 89 -165 2003年
  • 第7章 薬物代謝酵素誘導系を用いたバイオアッセイの環境生態研究
    産学官連携イノベーション創出事業費補助金、「ダイオキシン類・PCBの分解処理とバイオアッセイモニタリング」(課題番号12321)平成14年度研究成果総合研究報告書 81 -89 2003年
  • 薬物代謝酵素誘導系を用いたバイオアッセイの環境生態研究
    産学官連携イノベーション創出事業費補助金、「ダイオキシン類・PCBの分解処理とバイオアッセイモニタリング」(課題番号12321)平成14年度研究成果報告書 175 -206 2003年
  • 阿南 弥寿美, 國頭 恭, 池本 徳孝, 金 恩英, 岩田 久人, 田中 博之, 田辺 信介 Biomed. Res. Trace Elements 13 (4) 13(4)、266-267 -267 2002年12月
  • 酒井大樹, 岩田久人, KIM E-Y, 田辺信介, 馬場徳寿 日本内分泌かく乱化学物質学会研究発表会要旨集 5th 311 2002年11月
  • 岩田 久人, 金 恩英, 田辺 信介 生活衛生 46 (6) 46(6)、243-249 -249 2002年11月
  • カンボジアの都市ゴミ集積場における微量元素汚染と周辺住民への影響
    阿草 哲郎, 國頭 恭, Monirith In, 岩田 久人, 田辺 信介, Tana Touch Seang 環境ホルモン学会研究発表会要旨集 5回 399 -399 2002年11月
  • Accumulation of coplanar PCB congeners, and induction of cytochrome P450 in seabirds
    Proceedings of International Workshop on marine pollution by persistent organic pollutants (POPs) 65 -73 2002年
  • D-2 有害化学物質による地球規模の海洋汚染評価手法の構築に関する研究,(3)有害化学物質の地球規模での時空間変動機構および分解過程に関する研究
    地球環境研究総合推進費平成13年度研究成果―中間成果報告集―,環境省地球環境局研究調査室 74 -77 2002年
  • 平成13年度内分泌攪乱化学物質問題に関する日英共同研究 派遣研究者報告書
    平成13年度内分泌攪乱物質問題に関する日英共同研究報告書、(株)みなまた環境テクノセンター 185 -187 2002年
  • ブラジル沿岸に座礁した小型鯨類の有機塩素化合物汚染
    平成13年度内分泌攪乱物質問題に関する日英共同研究報告書、(株)みなまた環境テクノセンター 174 -187 2002年
  • 薬物代謝酵素の測定
    野生生物のダイオキシン類蓄積状況等調査マニュアル、(財)自然環境研究センター 130 -133 2002年
  • 薬物代謝酵素誘導系を用いたバイオアッセイによる環境生態研究
    革新的技術開発研究推進費補助金総合研究、「ダイオキシン類・PCBの分解処理とバイオアッセイモニタリング」(課題番号12321)平成13年度研究報告書 187 -213 2002年
  • Accumulation of coplanar PCB congeners, and induction of cytochrome P450 in seabirds
    Proceedings of International Workshop on marine pollution by persistent organic pollutants (POPs) 65 -73 2002年
  • 水圏生物への環境汚染物質の影響とその評価
    日本環境毒性学会主催、生態影響試験と評価に関するセミナー2001、「環境中化学物質の生態影響に関する最近の研究と動向」 11 -15 2001年
  • 薬物代謝酵素誘導を用いたバイオアッセイの環境研究への適用
    革新的技術開発研究推進費補助金総合研究、「ダイオキシン類・PCBの分解処理とバイオアッセイモニタリング」平成12年度研究報告書 27 -57 2001年
  • 有機塩素化合物による鳥類の汚染および影響の実態解明
    科学技術庁復興調整費、生活・社会基盤研究のうちの生活者ニーズ対応研究、「内分泌撹乱物質による生殖への影響とその作用機構に関する研究」研究報告書 2001年
  • ラット胎仔の脳及び生殖器官の発達・分化に及ぼすビスフェノールAの影響(Alterations in the differentiations and the developments of the central nervous system and reproductive organs of neonatal male rats following prenatal and lactational exposure to bisphenol A)
    Tateishi Yoko, Kim Eun-Young, Iwata Hisato, Shimamoto Yoshinori, Yoon Seok-Joo, Maruyama Yutaka, Chiba Issei, Ishizuka Mayumi, Kazusaka Akio, Fujita Shoichi 環境ホルモン学会研究発表会要旨集 3回 286 -286 2000年12月
  • 海棲哺乳類シトクロムP450遺伝子の同定と蛋白機能解析
    寺光 郁子, 千葉 一成, 岩田 久人, 田辺 信介, 藤瀬 良弘, 数坂 昭夫, 藤田 正一 日本獣医学会学術集会講演要旨集 129回 175 -175 2000年03月
  • 海洋汚染のマーカー酵素としてのアザラシ肝P450
    Chiba Issei, Sakakibara Akihito, Iwata Hisato, Tanabe Shinsuke, Kazusaka Akio, Fujita Shoichi The Journal of Toxicological Sciences 24 (4) 301 -301 1999年10月
  • 内因性ドーパミン作動性神経毒であるnorsalsolinolはPC12細胞においてドーパミンの分泌を阻害する
    Maruyama Yutaka, Suzuki Yuko, Teraoka Hiroki, Iwata Hisato, Kazusaka Akio, Fujita Shoichi The Journal of Toxicological Sciences 24 (4) 358 -358 1999年10月
  • Khlood El.Bohi M, Miyoshi Hiroyuki, Iwata Hisato, Kazusaka Akio, Kon Yasuhiro, Abou Hadid Ali H, Moustafe El. Kelish, Ghonim Mervat H, Fujita Shoichi Japanese Journal of Veterinary Research 47 (1-2) 13 -23 1999年08月 
    To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Darns were killed on the 20th. day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects : the fetal resorption amounted to similar to 60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were: absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.
  • PC12細胞のドパミン分泌に対する内因性ドパミン神経毒norsalsolinolの抑制性効果
    Maruyama Yutaka, Suzuki Yuko, Teraoka Hiroki, Iwata Hisato, Kazusaka Akio, Fujita Shoichi The Japanese Journal of Pharmacology 79 (Suppl.I) 49P -49P 1999年03月
  • Warfarinの反復投与が異物代謝酵素に及ぼす影響について
    出口 善行, 高橋 純子, 三好 啓子, 嶋本 良則, 斎藤 愛, 岩田 久人, 数坂 昭夫, 藤田 正一 日本獣医学会学術集会講演要旨集 127回 222 -222 1999年03月
  • 岩田 久人 哺乳類科学 = Mammalian Science 38 (1) 93 -95 1998年10月
  • 内因性dopaminergic neurotoxin,6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,のPC12細胞のドーパミン分泌に対する阻害効果
    Maruyama Yutaka, Shimamoto Yoshinori, Teraoka Hiroki, Iwata Hisato, Kazusaka Akio, Fujita Shoichi 家畜生化学 35 (2) 34 -34 1998年10月
  • イヌCytochromeP4502D15の分子生物学的手法を用いた機能解析
    田崎 隆史, 岩田 久人, 数坂 昭夫, 藤田 正一 日本獣医学会学術集会講演要旨集 126回 81 -81 1998年08月
  • 岩田 久人 水環境学会誌 = Journal of Japan Society on Water Environment 21 (7) 407 -411 1998年07月
  • 犬肝臓ミクロソーム及び発現型犬CYP2D15によるプロプラノロール代謝におけるR(+)及びS(-)選択性
    Tasaki Takafumi, Iwata Hisato, Kazusaka Akio The Journal of Biochemistry 123 (4) 747 -751 1998年04月
  • Indole-3-carbinol(I3C)による発癌抑制メカニズムに関する研究
    三好 啓子, 石塚 真由美, 岩田 久人, 数坂 照夫, 藤田 正一 日本獣医学会学術集会講演要旨集 125回 62 -62 1998年03月
  • 農薬(イソプロチオラン,ブタクロール,プレチラクロール)がラット肝薬物代謝能に与える影響
    石塚 真由美, 岩田 久人, 数坂 昭夫, 藤田 正一 日本獣医学会学術集会講演要旨集 125回 61 -61 1998年03月
  • Norsalsolinol脳室内投与によるParkinsonismの発現
    嶋本 良則, 丸山 豊, 星 英之, 田崎 隆史, 岩田 久人, 数坂 昭夫, 藤田 正一 日本獣医学会学術集会講演要旨集 125回 63 -63 1998年03月
  • Seasonal concetrations of PCBs and organochlorine pesticides (OCs) in the ambient air in the city of Gdansk, Poland.
    Organohalogen Compounds 39 219 -222 1998年
  • Polychlorinated biphenyls (PCBs) and organochlorines (OCs) in water of the Vistula River at the Kiezmark site, Poland.
    Organohalogen Compounds 39 215 -219 1998年
  • 内分泌撹乱化学物質による海棲哺乳類・鳥類への生体影響
    海洋と生物 117 (20) 270 -276 1998年
  • 残留性有機塩素化合物の水生生物への影響-特にダイオキシン類に着目して-
    水環境学会誌7月号 21 (7) 13 -17 1998年
  • 環境庁の「ダイオキシンのリスク評価」では野生動物を保護できない
    哺乳類科学 38 (1) 93 -95 1998年
  • Seasonal concetrations of PCBs and organochlorine pesticides (OCs) in the ambient air in the city of Gdansk, Poland.
    Organohalogen Compounds 39 219 -222 1998年
  • Polychlorinated biphenyls (PCBs) and organochlorines (OCs) in water of the Vistula River at the Kiezmark site, Poland.
    Organohalogen Compounds 39 215 -219 1998年
  • 知床半島に飛来したオオワシの有機塩素化合物汚染
    知床博物館研究報告 1 -7 1997年
  • 強毒性有機化合物汚染の指標動物 環境汚染を検知するためのバイオマーカーの有効性について
    岩田 久人, 石塚 真由美, 藤田 正一 獣医畜産新報 49 (8) 665 -669 1996年08月
  • 野生高等動物における有機スズ化合物の蓄積
    東京大学海洋研究所大槌臨海研究センター報告書第21号 (21) 61 -62 1996年
  • 強毒性有機化合物の指標動物-環境汚染を検知するためのバイオマーカーの有効性について-
    獣医畜産新報 (8月号) 665 -669 1996年
  • Environmental contamination by persistent toxic chemicals in Lake Baikal.
    In Proceeding of 6th International Conference on the Conservation and Management of Lake-Kasumigaura'95,Vol.2,Ibaragi,Japan, 1015 -1019 1995年
  • Environmental contamination by persistent toxic chemicals in Lake Baikal.
    In Proceeding of 6th International Conference on the Conservation and Management of Lake-Kasumigaura'95,Vol.2,Ibaragi,Japan, 1015 -1019 1995年
  • Global monitoring of toxic contaminants with use of fishing vessels.
    In Proceedings of International Workshop on Techniques of Persistent Organic Pollutant Measurements in Northern Environments,Waterloo,Ontario,Canada 27 -28 1994年
  • 有機塩素化合物によるバイカル湖の汚染
    文部省国際学術研究(1992-1993)研究成果報告書 42 -54 1994年
  • バイカル湖における有機塩素化合物汚染
    日本BICER協議会1993年度年報 29 -31 1994年
  • 有機スズ化合物による海洋汚染と生物への蓄積
    NETWORK 36 79 -88 1994年
  • Global monitoring of toxic contaminants with use of fishing vessels.
    In Proceedings of International Workshop on Techniques of Persistent Organic Pollutant Measurements in Northern Environments,Waterloo,Ontario,Canada 27 -28 1994年
  • Role of oceans in the fate of persistent organochlorines.
    In Proceedings of the International Symposium on Global Change (IGBP) 288 -297 1993年

受賞

  • 2011年07月 日本生態学会 第16回生態学琵琶湖賞
     
    受賞者: 岩田 久人
  • 2011年 Biwako Prize For Ecology
  • 2009年 15th Pollutants Response in Marine Organisms (PRIMO15) Best Presentation Award
  • 2006年 International Symposium 2006; Pioneering Studies of Young Scientists on Chemical Pollution and Environmental Changes Best Presentation Award
  • 2006年 International Symposium 2006; Pioneering Studies of Young Scientists on Chemical Pollution and Environmental Changes Best Presentation Award
  • 2005年 日本環境毒性学会奨励賞
     JPN
  • 2005年 13th Pollutants Response in Marine Organisms (PRIMO13) Best Presentation Award
  • 2005年 13th Pollutants Response in Marine Organisms (PRIMO13) Best Presentation Award
  • 2004年 日本環境毒性学会奨励賞
     JPN
  • 2004年 7th International Symposium on Cytochrome P-450 Biodiversity and Biotechnology 優秀ポスター賞
  • 2004年 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances ベストポスター賞
  • 2004年 7th International Symposium on Cytochrome P-450 Biodiversity and Biotechnology 優秀ポスター賞
  • 2004年 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances ベストポスター賞
  • 1994年 環境汚染と毒性学の分野における優秀論文賞(SCIPRESS) (Quintessence, Excellence in Environmental Contamination and Toxicology (SCIPRESS))
  • 1994年 QUINTESSENCE, Excellence in Environmental Contamination and Toxicology, SCIPRESS

共同研究・競争的資金等の研究課題

  • メコンデルタにおける水資源の汚染実態と高次生物ならびにヒトに対する毒性影響に関する研究
    研究期間 : 2003年 -2006年
  • Chemical Contamination in Mekong Delta and Their Toxic Effects on Higher Trophic Animals and Human
    研究期間 : 2003年 -2006年
  • 野生生物のエコトキシコゲノミクス・プロテオミクス
    科学技術振興調整費による中核的研究拠点(COE)育成
    研究期間 : 2002年 -2006年
  • 化学物質汚染による生態系への影響
    科学技術振興調整費による中核的研究拠点(COE)育成
    研究期間 : 2002年 -2006年
  • Ecotoxicogenomics and proteomics in wildlife
    SCF System for Establishment and Support of Center's of Excellence
    研究期間 : 2002年 -2006年
  • Toxic impacts of environmental contaminants in ecosystem
    SCF System for Establishment and Support of Center's of Excellence
    研究期間 : 2002年 -2006年
  • 毒性影響の種特異的感受性を決定する生体分子機構の解明
    科学研究費補助金
    研究期間 : 2001年 -2004年
  • Understanding of molecular mechanisms responsible for species-specific sensitivity of chemical toxicity
    Grant-in-Aid for Scientific Research
    研究期間 : 2001年 -2004年
  • 化学物質のリスクを評価するためのバイオアッセイ法の開発
    研究期間 : 2000年
  • 難分解性有機塩素化合物の地球規模での分布・動態・ゆくえ
  • Global distribution,dynamics and fate of persistent organochlorines

社会貢献活動

  • 第22回日本内分泌撹乱化学物質学会研究発表会
    期間 : 2019年12月12日 - 2019年12月13日
    役割 : 企画
    主催者・発行元 : 鑪迫 典久・岩田久人(大会実行委員長)
  • Japan-Korea Joint Symposium on Adverse Outcome Pathways: From Exposome to Phenotypic Effects
    期間 : 2019年07月09日 - 2019年07月11日
    役割 : 企画
    主催者・発行元 : 岩田久人(大会実行委員長)
  • 19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO19)
    期間 : 2017年06月30日 - 2017年07月03日
    役割 : 企画
    主催者・発行元 : 岩田久人(大会実行委員長)
  • International Symposium on Environmental Chemistry and Toxicology - To Accelerate a Global Network of Environmental Researchers
    期間 : 2016年03月19日 - 2016年03月19日
    役割 : 企画
    主催者・発行元 : 岩田久人(大会実行委員長)

愛媛大学教員活動実績

教育活動(B)

担当授業科目(B01)

  • 2019, 前期, 学部, 生物学ゼミナールⅠ
  • 2019, 前期, 学部, 生物学特別演習Ⅰ
  • 2019, 前期, 学部, 卒業研究Ⅰ
  • 2019, 前期, 学部, 生物化学基礎Ⅰ
  • 2019, 前期, 学部, 環境毒性学
  • 2019, 前期, 修士, 生物学ゼミナールI
  • 2019, 前期, 修士, 生物学ゼミナールⅢ
  • 2019, 前期, 修士, 生物学課題実験I
  • 2019, 前期, 修士, 生物学課題実験Ⅲ
  • 2019, 前期, 学部, 環境毒性学
  • 2019, 前期, 学部, 生物化学基礎Ⅰ
  • 2019, 前期, 学部, 環境毒性学


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