Understanding of molecular mechanisms of chemically-induced toxicities and risk evaluation using zebrafish

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H05334
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation and chemicals
• 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)
• Project Period (FY): 2015-04-01 – 2019-03-31
• 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

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.

Free Research Field

環境毒性学

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。