| Project/Area Number |
17K15862
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hygiene and public health
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| Research Institution | National Institute of Occupational Safety and Health,Japan |
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Principal Investigator |
Yanagiba Yukie 独立行政法人労働者健康安全機構労働安全衛生総合研究所, 化学物質情報管理研究センター有害性評価研究部, 上席研究員 (90467283)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | CYP2E1 / ジクロロプロパン / オルトトルイジン / 肝障害 / 中間代謝物 / 薬物代謝酵素 / 胆管がん / 膀胱がん / 経皮曝露 / 代謝物 / 1,2-ジクロロプロパン / 胆管癌 / 産業中毒 / 衛生 / 薬物代謝 / 生物学的モニタリング |
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| Outline of Final Research Achievements |
In recent years, multiple cases of bile duct cancer due to exposure to chemicals used at workplaces and the occurrence of bladder cancer at chemical plants have been reported. Although there is some knowledge of genotoxic effects among industrial chemicals used at workplaces, there are many substances for which the factors and mechanisms of carcinogenesis are still unknown. The mechanism of cholangiocarcinogenesis, which has occurred frequently in printing plants, has not yet been fully elucidated due to species differences. We suggested that CYP2E1 is involved in the metabolism of 1,2-dichloropropane (DCP) and dichloromethane (DCM), which were used as cleaning agents as causative agents of bile duct cancer, and o-toluidine, which has been reported as a causative agent of bladder cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
CYP2E1 は揮発性ハロゲン化化合物、芳香族化合物、アルコールなど非常に多くの化学物質の代謝に関わり、代謝過程産生される活性代謝物により毒性、変異原性、発がん等を誘発することが知られる薬物代謝酵素である。本研究では、CYP2E1に注目し、産業化学物質の遺伝毒性と遺伝毒性を有する中間代謝物の同定による毒性評価方法を確立させる。
この試験方法を用いた化学物質の毒性評価および中間代謝物の同定は、化学物質による労働災害や健康障害発生の予防（生物学的モニタリング手法の開発等）・対策に有用な情報を提供することを可能にする。
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