Understanding of molecular mechanisms of chemically-induced toxicities and risk evaluation using zebrafish
Project/Area Number |
15H05334
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Risk sciences of radiation and chemicals
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Research Institution | Obihiro University of Agriculture and Veterinary Medicine |
Principal Investigator |
Kubota Akira 帯広畜産大学, 畜産学部, 准教授 (60432811)
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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Keywords | トキシコロジー / ゼブラフィッシュ / 細胞内受容体 / 発生毒性 / 内分泌撹乱 / 環境汚染物質 / エストロゲン受容体 / シトクロムP450 / ビスフェノール類 / in silico解析 / リン酸エステル系難燃剤 / 化学物質 / CYP |
Outline of Final Research Achievements |
The present study aimed at understanding biological effects of a variety of chemicals and their molecular mechanisms, with particular emphasis on signaling pathways involving cellular receptors, using zebrafish as a model organism. Some of the biological effects identified include cytochrome P450 induction, cardiovascular toxicity, and endocrine disruption, through the cellular receptors such as pregnane X receptor (PXR), aryl hydrocarbon receptor type 2 (AHR2) and estrogen receptors (ERs). The current study also suggest that in silico simulations of interaction between chemicals and ER subtypes can predict in vivo potency of the ER-mediated response by untested chemical substances.
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Academic Significance and Societal Importance of the Research Achievements |
動物愛護の観点から、化学物質の有害性評価において動物実験代替法の利用を促進する活動が拡大する中で、ゼブラフィッシュを用いた本研究の成果は、動物愛護に寄与し多数の化学物質をハイスループットに評価したものとして学術的・社会的意義は大きい。さらに本研究の成果は、細胞内受容体を介した作用が疑われる医薬品等の安全性評価や環境汚染物質の生態毒性試験法として発展的に活用することも期待され、医療・環境分野における化学物質リスク評価の指針となるだけでなく、わが国の化学物質管理政策にも資すると考えられる。
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Report
(5 results)
Research Products
(46 results)
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[Journal Article] Transcriptional profiling of cytochrome P450 genes in the liver of adult zebrafish, <i>Danio rerio</i>2019
Author(s)
Akira Kubota, Yusuke K. Kawai, Natsumi Yamashita, Jae Seung Lee, Daisuke Kondoh, Shuangyi Zhang, Yasunobu Nishi, Kazuyuki Suzuki, Takio Kitazawa, Hiroki Teraoka
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Journal Title
The Journal of Toxicological Sciences
Volume: 44
Issue: 5
Pages: 347-356
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access
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[Journal Article] Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner2016
Author(s)
Wincent, E., Kubota, A., Timme-Laragy, A. R., Jönsson, M. E., Hahn, M. E. and Stegeman, J. J.
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Journal Title
Biochemical Pharmacology
Volume: 110-111
Pages: 117-129
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Protective effect of prostacyclin against pre-cardiac edema caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin and a thromboxane receptor agonist in developing zebrafish2016
Author(s)
Nijoukubo, D., Tanaka, Y., Okuno, Y., Yin, G., Kitazawa, T., Peterson, R. E., Kubota, A. and Teraoka, H.
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Journal Title
Chemosphere
Volume: 156
Pages: 111-117
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Functional characterization of zebrafish cytochrome P450 1 family proteins expressed in yeast2015
Author(s)
Stegeman, J. J., Behrendt, L., Woodin, B. R., Kubota, A., Lemaire, B., Pompon, E., Goldstone, J. V. and Urban, P.
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Journal Title
Biochimica et Biophysica Acta
Volume: 1850(11)
Issue: 11
Pages: 2340-2352
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Characterization of a Pxr-null zebrafish2016
Author(s)
Matthew C. Salanga, Akira Kubota, Benjamin Lemaire, Rachel Harbeitner, Daniel Gusenleitner, Stefano Monti, John J. Stegeman, Jared V. Goldstone
Organizer
55th Annual Meeting of Society of Toxicology
Place of Presentation
ニューオーリンズ(米国)
Year and Date
2016-03-13
Related Report
Int'l Joint Research
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[Presentation] The PXR “gene battery” in zebrafish2015
Author(s)
Jared V. Goldstone, Rachel Harbeitner, Akira Kubota, Benjamin Lemaire, John J. Stegeman
Organizer
18th International symposium on Pollutant Responses in Marine Organisms
Place of Presentation
トロンハイム(ノルウェー)
Year and Date
2015-05-24
Related Report
Int'l Joint Research
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