| Project/Area Number |
26460817
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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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 |
Wang Rui-Sheng 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, 産業毒性・生体影響研究グループ, 部長 (10321895)
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| Co-Investigator(Kenkyū-buntansha) |
須田 恵 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, 産業毒性・生体影響研究グループ, 上席研究員 (90415969)
柳場 由絵 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, 産業毒性・生体影響研究グループ, 主任研究員 (90467283)
鈴木 哲矢 広島大学, 医歯薬保健学研究院(薬), 助教 (20573950)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 職業性胆管癌 / 1,2-ジクロロプロパン / 遺伝毒性 / 代謝活性化 / ヒストンH2AXリン酸化 / 活性酸素種 / １,２－ジクロロプロパン / 代謝 / ALDH2 / CYP2E1 |
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| Outline of Final Research Achievements |
1,2-Dichloropropane (DCP) is suspected to induce the cholangiocarcinoma among workers in an off-set printing company. Using experimental animals and human orriginated cell lines, we found that DCP can induce DNA damages, and CYP2E1 and other enzymes are invovled in its metabolic activation and genotoxicity expression. After DCP exposure, methyl glyoxal（MG）can be detected with high concentrations in bile, and this intermediate metabolite shows high genotoxicity at very low concentrations. Besides, DCP exposure increases the levels of intracellular reactive oxygen species (ROS), but addition of antioxidant attenuated the ROS level as well as DNA damages. These results suggest that DCP is metabolized by CYP2E1-mediated pathway and MG and ROS produced in the metabolic processes may contribute to the induction of occupational cholangiocarcinoma by this solvent.
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