Clarification of factors governing sensitivity of disruption of intracellular receptor-xenobiotic metabolizing enzyme signaling pathways by chemical substances

2013 Fiscal Year Final Research Report

• Project/Area Number: 21221004
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Ehime University
• Principal Investigator: IWATA HISATO 愛媛大学, 沿岸環境科学研究センター, 教授 (10271652)
• Co-Investigator(Kenkyū-buntansha): AGUSA Tetsuro 愛媛大学, 沿岸環境科学研究センター, 特任助教 (50403853) ; MIYAZAKI Tatsuhiko 岐阜大学, 附属病院, 教授 (80239384) ; SUZUKI Ken-ichi 広島大学, 大学院理学研究科, 特任助教 (90363043) ; ISHIBASHI Hiroshi 尚絅大学短期大学部, 食物栄養学科, 准教授 (90403857) ; NOSE Masato 愛媛大学, 大学院医学系研究科, 客員研究員 (70030913)
• Co-Investigator(Renkei-kenkyūsha): HIRANO Masashi 愛媛大学, 沿岸環境科学研究センター, 沿岸環境科学研究センター・学振特別研究員(PD) (20554471)
• Project Period (FY): 2009-05-11 – 2014-03-31
• Keywords: 化学物質 / 細胞内受容体 / シトクロムP450 / 感受性 / 野生動物

Research Abstract

The achievements of this study are summarized as follows;
1) for the screening of toxic environmental pollutants, we succeeded in developing in vitro assay systems that intracellular receptor proteins of wild animals are expressed, 2) the intracellular receptor proteins showed species- and isoform-specific responses to the exposure to toxic environmental pollutants, 3) the in vitro assay systems enabled us to assess the risk incorporating the interspecies differences in susceptibility in some wild populations, 4) certain amino acid residues that were evolutionary mutated contribute to the ligand interaction of intracellular receptors and cytochrome P450, and 5) there are factors responsible for the susceptibility other than intracellular receptors and cytochrome P450.

Research Products

• [Journal Article] Molecular and functional characterization of a novel aryl hydrocarbon receptor isoform, AHR1β in the chicken (Gallus gallus) (2013)
  • Author(s): Lee, J. S., Iwabuchi, K., Nomaru, K., Nagahama, N., Kim, E. Y., Iwata, H
  • Journal Title: Toxicological Sciences Volume: 136(2) Pages: 450-466
  • DOI: 10.1093/toxsci/kft192
  • Peer Reviewed
• [Journal Article] Alternative in vitro approach for assessing AHR-mediated CYP1A induction by dioxins in wild cormorant (Phalacrocorax carbo) population (2013)
  • Author(s): Thuruthippalli, L. M., Kubota, A. Kim, E. Y., Iwata, H
  • Journal Title: Environmental Science and Technology Volume: 47(12) Pages: 6656-6663
  • DOI: 10.1021/es401155g
  • Peer Reviewed
• [Journal Article] Potencies of red seabream AHR1-and AHR2-mediated transctivation by dioxins : implication of both AHRs in dioxin toxicity (2013)
  • Author(s): Bak, S. M., Iida, M., Hirano, M., Iwata, H., Kim, E. Y
  • Journal Title: Environmental Science and Technology Volume: 47(6) Pages: 2877-2885
  • DOI: 10.1021/es304423w
  • Peer Reviewed
• [Journal Article] Quantitative analysis of the interaction of constitutive androstane receptor with chemicals and steroid receptor coactivator 1 using surface plasmon resonance biosensor systems : a case study of the Baikal seal and the mouse (2013)
  • Author(s): Dau, P. T., Sakai, H., Hirano, M., Ishibashi, H., Tanaka, Y., Kameda, K., Fujino, T., Kim, E. Y., Iwata, H
  • Journal Title: Toxicological Sciences Volume: 131(1) Pages: 116-127
  • DOI: 10.1093/toxsci/kfs288
  • Peer Reviewed
• [Journal Article] Toxicokinetics of dioxins and other organochlorine compounds in Japanese people : association with hepatic CYP1A2 expressioin levels (2013)
  • Author(s): Wananabe, M. X., Kunisue, T., Ueda, N., Nose, M., Tanabe, S., Iwata, H
  • Journal Title: Environment International Volume: 53 Pages: 53-61
  • DOI: 10.1016/j.envint.2012.12.008
  • Peer Reviewed
• [Journal Article] Sex differences in the accumulation of chlorinated dioxins in the cormorant (Phalacrocorax carbo) : implication of hepatic sequestration in the maternal transfer (2013)
  • Author(s): Kubota, A., Yoneda, K., Tanabe, S., Iwata, H
  • Journal Title: Environmental Pollution Volume: 178 Pages: 300-305
  • DOI: 10.1016/j.envpol.2013.03.001
  • Peer Reviewed
• [Journal Article] In vitro transactivation potencies of black-footed albatross (Phoebastria nigripes) AHR1 and AHR2 by dioxins to predict CYP1A expression in the wild population (2012)
  • Author(s): Thuruthippallil, L. M., Kim, E. Y., Ishibashi, H., Iwata, H
  • Journal Title: Environmental Science and Technology Volume: 46(1) Pages: 525-533
  • DOI: 10.1021/es2028263
  • Peer Reviewed
• [Journal Article] Individual variations in arsenic metabolism in Vietnamese : the association with arsenic exposure and GSTP1 genetic polymorphism (2012)
  • Author(s): Agusa, T., Kunito, T., Tue, N. M., Lan, V. T., Fujihara, J., Takeshita, H., Minh, T. B., Trang, P. T. K., Takahashi, S., Viet, P. H., Tanabe, S., Iwata, H
  • Journal Title: Metallomics : Integrated Biometal Science Volume: 4(1) Pages: 91-100
  • DOI: 10.1039/c1mt00133g
  • Peer Reviewed
• [Journal Article] Molecular and functional characterization of aryl hydrocarbon receptor nuclear translocator 1 (ARNT1) and ARNT2 in chicken (Gallus gallus) (2011)
  • Author(s): Lee, J. S., Kim, E. Y., Iwabuchi, K., Iwata, H
  • Journal Title: Comparative Biochemistry and Physiology, Part C Volume: 153(3) Pages: 269-279
  • DOI: 10.1016/j.cbpc.2010.11.005
  • Peer Reviewed
• [Journal Article] Cytochrome P450 CYP2 genes in the common cormorant : evolutionary relationships with 130 diapsid CYP2 clan sequences and chemical effects on their expression (2011)
  • Author(s): Kubota, A., Stegeman, J. J., Goldstone, J. V., Nelson, D. R., Kim, E. Y., Tanabe, S., Iwata, H
  • Journal Title: Comparative Biochemistry and Physiology, Part C Volume: 153(3) Pages: 280-289
  • DOI: 10.1016/j.cbpc.2010.11.006
  • Peer Reviewed
• [Journal Article] Integrative assessment of potential effects of dioxins and related compounds in wild Baikal seals (Pusa sibirica) : application of microarray and biochemical analyses (2011)
  • Author(s): Hirakawa, S., Imaeda, D., Nakayama, K., Udaka, M., Kim, E. Y., Kunisue, T., Ogawa, M., Matsuda, T., Matsui, S., Petrov, E. A., Batoev, V. B., Tanabe, S., Iwata, H
  • Journal Title: Aquatic Toxicology Volume: 105(1-2) Pages: 89-99
  • DOI: 10.1016/j.aquatox.2011.05.007
  • Peer Reviewed
• [Journal Article] Evaluation of relative potencies for in vitro transactivation of the Baikal seal aryl hydrocarbon receptor by dioxin-like compounds (2011)
  • Author(s): Kim, E. Y., Suda, T., Tanabe, S., Batoev, V. B., Petrov, E. A., Iwata, H
  • Journal Title: Environmental Science and Technology Volume: 45(4) Pages: 1652-1658
  • DOI: 10.1021/es102991s
  • Peer Reviewed
• [Journal Article] Transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome proliferatoractivated receptor α by perfluoroalkyl carboxylates and sulfonates : estimation of PFOA induction equivalency factors (2011)
  • Author(s): Ishibashi, H., Kim, E. Y., Iwata, H
  • Journal Title: Environmental Science and Technology Volume: 45(7) Pages: 3123-3130
  • DOI: 10.1021/es103748s
  • Peer Reviewed
• [Journal Article] Molecular and functional characterization of aryl hydrocarbon receptor repressor from the chicken (Gallus gallus) : interspecies similarities and differences (2011)
  • Author(s): Lee, J. S., Kim, E. Y., Nomaru, K., Iwata, H
  • Journal Title: Toxicological Sciences Volume: 119(2) Pages: 319-334
  • DOI: 10.1093/toxsci/kfq336
  • Peer Reviewed
• [Journal Article] Dioxin-like and perfluorinated compounds in pigs in an Indian open waste dumping site : toxicokinetics and effects on hepatic cytochrome P450 and blood plasma hormones (2010)
  • Author(s): Watanabe, M. X., Kunisue, T., Tao, L., Kannan, K., Subramanian, An., Tanabe, S., Iwata, H
  • Journal Title: Environmental Toxicology and Chemistry Volume: 29(7) Pages: 1551-1560
  • DOI: 10.1002/etc.189
  • Peer Reviewed
• [Journal Article] Hepatic CYP1A introduction by chlorinated dioxins and related compounds in the endangered black-footed albatross from the North Pacific (2010)
  • Author(s): Kubota, A., Watanabe, M., Kunisue, T., Kim, E. Y., Tanabe, S., Iwata, H
  • Journal Title: Environmental Science & Technology Volume: 44(9) Pages: 3559-3565
  • DOI: 10.1021/es1000177
  • Peer Reviewed
• [Journal Article] Effects of in ovo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic AHR/ARNTCYP1A signaling pathways in common cormorants (Phalacrocorax carbo) (2010)
  • Author(s): Iwata, H., Nagahama, N., Kim, E. Y., Watanabe, M. X., Sudo, A
  • Journal Title: Comparative Biochemistry and Physiology, Part C Volume: 152(2) Pages: 224-231
  • DOI: 10.1016/j.cbpc.2010.04.010
  • Peer Reviewed
• [Journal Article] Transactivation potencies of Baikal seal constitutive active/androstane receptor by persistent organic pollutants and brominated flame retardants (2009)
  • Author(s): Sakai, H., Kim, E. Y., Petrov, E. A., Tanabe, S., Iwata, H
  • Journal Title: Environmental Science and Technology Volume: 43(16) Pages: 6391-6397
  • DOI: 10.1021/es901120r
  • Peer Reviewed
• [Journal Article] Alkoxyresorufin (methoxy-, ethoxy-, pentoxy- and benzyloxyresorufin) O-dealkylase activities by in vitro-expressed cytochrome P450 1A4 and 1A5 from common cormorant (Phalacrocorax carbo) (2009)
  • Author(s): Kubota, A., Kim, E. Y., Iwata, H
  • Journal Title: Comparative Biochemistry and Physiology - C Toxicology and Pharmacology Volume: 149(4) Pages: 544-551
  • DOI: 10.1016/j.cbpc.2008.12.004
  • Peer Reviewed
• [Journal Article] Dioxin activation of CYP1A5 promoter/ enhancer regions from two avian species, common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus) : association with aryl hydrocarbon receptor 1 and 2 isoforms (2009)
  • Author(s): Lee, J. S., Kim, E. Y., Iwata, H
  • Journal Title: Toxicology and Applied Pharmacology Volume: 234(1) Pages: 1-13
  • DOI: 10.1016/j.taap.2008.09.007
  • Peer Reviewed
• [Presentation] 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 (2013)
  • Author(s): 岩田久人、平野将司、Kim, Eun-Young
  • Organizer: 環境ホルモン学会 第16回研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2013-12-12
  • Invited
• [Presentation] Development of ecotoxicological tools for the assessment of susceptibility and risk (2012)
  • Author(s): Iwata, H
  • Organizer: SETAC Asia Pacific 2012 Meeting
  • Place of Presentation: Kumamoto, Japan
  • Year and Date: 2012-09-26
  • Invited
• [Presentation] 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 (2012)
  • Author(s): 岩田久人
  • Organizer: 第39回日本毒性学会学術年会
  • Place of Presentation: 仙台
  • Year and Date: 2012-07-17
  • Invited
• [Presentation] In vitro approaches for assessing the risk of toxic contaminants in wildlife (2011)
  • Author(s): Iwata, H. and Kim, E. Y
  • Organizer: 4^<th> International Conference on Environmental Health Science
  • Place of Presentation: Incheon, Korea
  • Year and Date: 2011-10-17
  • Invited
• [Presentation] Chemical impacts on aquatic birds and mammals : xenobiotic receptor-based risk assessment (2010)
  • Author(s): Iwata, H. and Kim, E. Y
  • Organizer: The 4^<th> Bilateral Seminar Italy-Japan, Physical and Chemical Impacts on Marine Organisms - for Conservation of Biodiversity and Sustainability
  • Place of Presentation: Nagakute, Japan
  • Year and Date: 2010-10-25
  • Invited
• [Book] 3.6.バイオマーカー, 環境毒性学, 渡邉 泉・久野勝治編 (2011)
  • Author(s): 岩田久人
  • Total Pages: 137-147
  • Publisher: 朝倉書店
• [Book] 第5章生物反応を利用して化学物質汚染の危険性を検知する, 分子でよむ環境汚染, 鈴木聡編著 (2009)
  • Author(s): 岩田久人・金 恩英
  • Total Pages: 122-157
  • Publisher: 第東海大学出版会
• [Remarks] ①愛媛大学沿岸環境科学研究センター岩田 研究室のサイト 日本語版
  • URL: http://ecotoxiwata.jp/
• [Remarks] ①愛媛大学沿岸環境科学研究センター岩田 研究室のサイト 英語版
  • URL: http://ecotoxiwata.jp/en/index.html
• [Remarks] ②基盤研究(S)のサイト
  • URL: http://ecotoxiwata.jp/sr-s.html
• [Remarks] ③愛媛大学最先端研究紹介サイト
  • URL: http://www.ehime-u.ac.jp/research/infinity/index.html
• [Remarks] ①3rd International Conference on Proteomics and Bioinformatics, Best Poster Award, Maria Claret Lauan(研究協力者), 2013年7月, 米国・フィラデルフィア. 表彰等
• [Remarks] ②51^<th> Annual Meeting of Society of Toxicology, The Robert J. Rubin Student Travel Award, Thuruthippallil Leena Mol(研究協力者), 2012年3月, 米国・サンフランシスコ. 表彰等
• [Remarks] ③第17回ヒ素シンポジウム, 奨励賞, 阿草哲郎(研究分担者), 2011年11月, 茨城県・つくば市. 表彰等
• [Remarks] ④第16回生態学琵琶湖賞, 岩田久人(研究代表者), 2011年7月, 滋賀県・大津市 表彰等
• [Remarks] ⑤Toxicological Sciences, Highlighted article(Lee, J.S., Kim, E.Y., Nomaru, K., Iwata, H. (2011): Molecular and functional characterization of aryl hydrocarbon receptor repressor from the chicken (Gallus gallus): interspecies similarities and differences. Toxicological Sciences, 119(2), 319-334), 2011年2月. 表彰等
• [Remarks] ⑥15th International Symposium on Pollutants Responses in Marine Organisms(PRIMO), Best Presentation Award, Thuruthippallil Leena Mo(l 研究協力者), 2009年5月, フランス・ボルドー. 表彰等