High-throughput risk assay of chemicals using a nuclear receptor, CAR from aquatic animals

2008 Fiscal Year Final Research Report

• Project/Area Number: 17208030
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Boundary agriculture
• Research Institution: Ehime University
• Principal Investigator: IWATA Hisato Ehime University, 沿岸環境科学研究センター, 教授 (10271652)
• Co-Investigator(Kenkyū-buntansha): 金 恩英 愛媛大学, 沿岸環境科学研究センター, グローバルCOE准教授 (70419513) ; 田辺 信介 愛媛大学, 沿岸環境科学研究センター, 教授 (60116952)
• Project Period (FY): 2005 – 2008
• Keywords: constitutive androstane receptor / PCB / DDT / POPs / アザラシ

Research Abstract

バイカルアザラシの核内受容体constitutive androstane receptor(CAR)と反応する化学物質をスクリーニングしたところ、PCB やDDT はCARとよく反応することが明らかとなった。これらの結果から、過去にラットやマウスなどの齧歯類で得られたCAR に関する知見は、難分解性有機汚染物質(POPs)に対する反応差の観点から、水棲哺乳類などの野生生物に単純に外挿できないことがわかった。一方で本研究の結果は、各野生生物種のCAR遺伝子を用いて構築したin vitroアッセイ系により、対象種固有のPOPsのリスクが評価できる可能性を示した。

Research Products

• [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 234 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Catalytic function of avian cytochrome P450 1A4 and 1A5 (CYP1A4 and CYP1A5) enzymes heterologously expressed using in vitro yeast system (2008)
  • Author(s): Kubota, A., Iwata, H. and Kim, E.Y.
  • Journal Title: Marine Environmental Research 66(1) Pages: 154-155
  • Peer Reviewed
• [Journal Article] Contamination and effects of perfluorochemicals in Baikal seal. 1. residue level, tissue distribution, and temporal trend (2008)
  • Author(s): Ishibashi, H., Iwata, H., Kim, E.Y., 他7名
  • Journal Title: Environmental Science & Technology 42 Pages: 2295-2301
  • Peer Reviewed
• [Journal Article] Contamination and effects of perfluorochemicals in Baikal seal. 2. molecular characterization, expression level, and transcriptional activation of peroxisome proliferator-activated receptor α (2008)
  • Author(s): Ishibashi, H., Iwata, H., Kim, E.Y., 他5名
  • Journal Title: Environmental Science & Technology 42 Pages: 2302-2308
  • Peer Reviewed
• [Journal Article] Molecular characterization of cytochrome P450 1A1, 1A2, and 1B1, and effects of polychlorinated dibenzo- p-dioxin, dibenzofuran, and biphenyl congeners on their hepatic expression in Baikal seal (2007)
  • Author(s): Hirakawa, S., Iwata, H., Takeshita, Y., Kim, E.Y., 他6名
  • Journal Title: Toxicological Sciences 97 Pages: 318-335
  • Peer Reviewed
• [Journal Article] Functional characterization and evolutionary history of two aryl hydrocarbon receptor isoforms (AhR1 and AhR2) from Avian Species (2007)
  • Author(s): Yasui, T., Kim, E.Y., Iwata, H., 他4名
  • Journal Title: Toxicological Sciences 99 Pages: 101-117
  • Peer Reviewed
• [Journal Article] Identification and hepatic expression profiles of cytochrome P450 1-4 isozymes in common minke whales (2007)
  • Author(s): Niimi, S., Kim, E.Y., Iwata, H., Watanabe, M.X., 他3名
  • Journal Title: Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 147(4) Pages: 667-81
  • Peer Reviewed
• [Journal Article] Molecular characterization and tissue distribution of aryl hydrocarbon receptor nuclear translocator isoforms, ARNT1 and ARNT2, and identification of novel splice variants in common cormorant (Phalacrocorax carbo) (2007)
  • Author(s): Lee, J.S., Kim, E.Y., Iwata, H., Tanabe, S.
  • Journal Title: Comparative Biochemistry and Physiology Part C Toxicology and Pharmacology 145(3) Pages: 379-93
  • Peer Reviewed
• [Journal Article] Chemical contamination in aquatic ecosystems (2007)
  • Author(s): Iwata, H., Kim, E.Y., 他4名
  • Journal Title: Yakugaku Zasshi 127(3) Pages: 417-428
  • Peer Reviewed
• [Journal Article] Toxic effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in developing red seabream (Pagrus major) embryo : an association of morphological deformities with AHR1, AHR2 and CYP1A expressions (2007)
  • Author(s): Yamauchi, M., Kim, E.Y., Iwata, H., Shima, Y. and Tanabe, S.
  • Journal Title: Aquatic Toxicology 40 Pages: 6919-6927
  • Peer Reviewed
• [Journal Article] Cytochrome P450 1A4 and 1A5 in common cormorant (Phalacrocorax carbo) : evolutionary relationships and functional implications associated with dioxin and related compounds (2006)
  • Author(s): Kubota, A., Iwata, H., Goldstone, H. M. H., Kim, E. Y., Stegeman, J. J. and Tanabe, S.
  • Journal Title: Toxicological Sciences 92 Pages: 394-408
  • Peer Reviewed
• [Journal Article] Congener-specific toxicokinetics of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in black-eared kites : cytochrome P4501A-dependent hepatic sequestration (2006)
  • Author(s): Kubota, A., Iwata, H., 他3名
  • Journal Title: Environmental Toxicology and Chemistry 25 Pages: 1007-1016
  • Peer Reviewed
• [Journal Article] Constitutive androstane receptor (CAR) as a potential sensing biomarker of persistent organic pollutants (POPs) in aquatic mammal : molecular characterization, expression level and ligand profiling in Baikal seal (2006)
  • Author(s): Sakai, H., Iwata, H., Kim, E.Y., 他5名
  • Journal Title: Toxicological Sciences 94 Pages: 57-70
  • Peer Reviewed
• [Journal Article] PCDDs, PCDFs, and coplanar PCBs in wild terrestrial mammals from Japan : congener specific accumulation and hepatic sequestration (2006)
  • Author(s): Kunisue, T., Watanabe, M.X., Iwata, H., 他4名
  • Journal Title: Environmental Pollution 140(3) Pages: 525-535
  • Peer Reviewed
• [Journal Article] Bioaccumulation of organochlorines in crows from Indian open waste dumping site : evidence for direct transfer of dioxin-like congeners from the contaminated soil (2005)
  • Author(s): Watanabe, M.X., Iwata, H., 他3名
  • Journal Title: Environmental Science and Technology 39 Pages: 4421-4430
  • Peer Reviewed
• [Journal Article] Hepatic CYP1A induction by dioxin-like compounds, and congener-specific metabolism and sequestration in wild common cormorants from Lake Biwa Japan. (2005)
  • Author(s): Kubota, A., Iwata, H., Tanabe, S., Yoneda, K. and Tobata, S.
  • Journal Title: Environmental Science and Technology 39 Pages: 3611-3619
  • Peer Reviewed
• [Journal Article] Induction of cytochrome P450 1A5 mRNA, protein and enzymatic activities by dioxin-like compounds, and congener-specific metabolism and sequestration in the liver of wild jungle crow from Tokyo, Japan (2005)
  • Author(s): Watanabe, M.X., Iwata, H., Kim, E.Y., 他3名
  • Journal Title: Toxicolgical Sciences 88 Pages: 384-399
  • Peer Reviewed
• [Journal Article] Molecular cloning and mRNA expression of cytochrome P4501A1 and 1A2 in the liver of common minke whales ( Balaenoptera acutorostrata) (2005)
  • Author(s): Niimi, S., Watanabe, M.X., Kim, E.Y., Iwata, H., Yasunaga, G., Fujise, Y. and Tanabe, S.
  • Journal Title: Marine Pollution Bulletin 51 Pages: 784-793
  • Peer Reviewed
• [Journal Article] Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator expression in Baikal seal and association with 2,3,7,8-TCDD toxic equivalents and CYP1 expression levels (2005)
  • Author(s): Kim, E.Y., Iwata, H., 他5名
  • Journal Title: Comparative Biochemistry and Physiology Part C Toxicology and Pharmacology 141 Pages: 281-291
  • Peer Reviewed
• [Journal Article] Molecular characterization of the aryl hydrocarbon receptors (AHR1 and AHR2) from red seabream ( Pagrus major) (2005)
  • Author(s): Yamauchi, M., Kim, E.Y., Iwata, H. and Tanabe, S.
  • Journal Title: Comparative Biochemistry and Physiology Part C Toxicology and Pharmacology 141 Pages: 177-187
  • Peer Reviewed
• [Presentation] バイカルアザラシCYP2BおよびCYP3Aプロモーター/エンハンサー領域の分子特性とPOPsによる転写活性化能 (2008)
  • Author(s): 酒井大樹・岩田久人・金恩英・Petrov, E. A.・田辺信介
  • Organizer: 環境ホルモン学会第11回研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-13
• [Presentation] Molecular characterization of Baikal seal CYP2B/3A promoter/enhancer regions and their transactivation potencies by POPs (2008)
  • Author(s): Sakai, H., Iwata, H., Kim, E. Y., Petrov, E. A. and Tanabe, S.
  • Organizer: 5^<th> SETAC World Congress
  • Place of Presentation: Sydney, Australia(Abstract CD)
  • Year and Date: 2008-08-04
• [Presentation] Effects of dioxins in wild Baikal seals : an implication from a toxicogenomic approach (2008)
  • Author(s): Hirakawa, S., Imaeda, D., Nakayama, K., Kim, E. Y., Kunisue, T., Tanabe, S., Petrov, E. A., Batoev, V. B. and Iwata, H.
  • Organizer: 5^<th> SETAC World Congress
  • Place of Presentation: Sydney, Australia(Abstract CD)
  • Year and Date: 2008-08-04
• [Presentation] Relative Potencies of Individual Dioxin-Like Compounds for In Vitro Cytrochrome P450 1A1 Transactivation of Aryl Hydrocarbon Receptor from Baikal Seal (2008)
  • Author(s): Iwata, H., Kim, E.Y., Suda, T., Tanabe, S. and Petrov, E.A.
  • Organizer: Society of Toxicology 47^<th> Annual Meeting. Washington
  • Place of Presentation: Seattle, USA, Program
  • Year and Date: 2008-03-18
• [Presentation] Low Induction Potencies of Cytochrome P450 2B and 3A by Persistent Organic Pollutants in Baikal Seal ( Pusa sibirica) (2008)
  • Author(s): Sakai, H., Iwata, H., Kim, E.Y., Petrov, E.A. and Tanabe, S.
  • Organizer: Biological Responses to Chemical Pollutants : Toward Establishing an Asian Network of Environmental Toxicology
  • Place of Presentation: Matsuyama, Japan, Abstract Book
  • Year and Date: 2008-03-06
• [Presentation] Species diversity of AHR-CYP1A signaling pathways : Toward risk assessment of dioxin-like compounds in wildlife (2007)
  • Author(s): Iwata, H. and Kim, E. Y.
  • Organizer: International Symposium on the Environmental Risks of Chemicals
  • Place of Presentation: Saitama, Japan, Program and Abstracts
  • Year and Date: 2007-12-10
• [Presentation] Inter-species and -isoform differences in signaling pathways of aryl hydrocarbon receptors : A casestudy of fish and bird (2007)
  • Author(s): Iwata, H. and Kim, E. Y.
  • Organizer: Special Seminar in Hanyang University
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2007-11-21
• [Presentation] Transactivation potentials of constitutive androstane/active receptor by persistent organic pollutants and brominated flameretardants : a comparative study of Baikal Seal ( Pusa sibirica) and mouse. (2007)
  • Author(s): Sakai, H., Iwata, H., Kim, E.Y., Petrov, E. A. and Tanabe, S.
  • Organizer: DIOXIN 2007 International Symposium
  • Place of Presentation: Tokyo, Japan Abstracts Book
  • Year and Date: 2007-09-03
• [Presentation] Xenobiotic ligand profiles of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in Baikal seal ( Pusa sibirica) (2007)
  • Author(s): Iwata, H., Sakai, H., Kadota, M., Kim, E. Y., Tanabe, S., Batoev, V. B. and Petrov, E. A
  • Organizer: 14^<th> International Symposium Pollutant Responses in Marine Organisms
  • Place of Presentation: Brazil Abstruct Book
  • Year and Date: 2007-05-09
• [Presentation] Contamination by perfluorinated compounds and effects on peroxisome proliferators-activated receptor alpha-Cytochrome P450 4A signaling pathway in Baikal seal ( Pusa sibirica). (2007)
  • Author(s): Iwata, H., Ishibashi, H., Kim, E. Y., Tao, L., Kannan, K., Tanabe, S., Batoev, V. B. and Petrov, E. A.
  • Organizer: 14^<th> International Symposium Pollutant Responses in Marine Organisms
  • Place of Presentation: Brazil Abstract Book
  • Year and Date: 2007-05-09
• [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, 分子で読む環境汚染 (2008)
  • Author(s): 岩田久人・金恩英
  • Total Pages: 122-157
  • Publisher: 鈴木聡編,東海大学出版会
• [Book] 日本環境毒性学会, 畠山成久編, アイピーシー (2006)
  • Author(s): 岩田久人
  • Total Pages: 233-252
  • Publisher: 第6章バイオマーカーによる影響評価, 化学物質の生態リスク評価と規制-農薬編-