| Project/Area Number |
18K10061
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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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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | National Institute for Environmental Studies |
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Principal Investigator |
SUZUKI Takehiro 国立研究開発法人国立環境研究所, 環境リスク・健康研究センター, 主任研究員 (60425494)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ヒ素 / 妊娠期曝露 / 後発影響 / 肝実質細胞 / RNA-Seq / RNA-seq / 肝星細胞 |
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| Outline of Final Research Achievements |
Exposure to environmental chemicals during fetal development can increase the risk of various late-onset adverse effects. We have previously showed that gestational arsenic exposure of C3H mice induces increased hepatic tumor incidence in the F1 and F2 male offspring. In this study, to examine the mechanisms of increased hepatic tumor increase in the F2 male mice gestationally exposed to arsenic, we isolated hepatocytes and hepatic stellate cells from liver tissue of mice and analyzed the gene expression changes in hepatocytes and hepatic stellate cells of F2 males by RNA-sequencing (RNA-Seq) and real-time RT-PCR. The current study suggests that changes in gene expression associated with lipid accumulation, gluconeogenesis suppression, and/or increased oxidative stress in hepatocytes are involved in increased hepatic tumor incidence in the F2 generation.
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| Academic Significance and Societal Importance of the Research Achievements |
有害物質に脆弱と考えられる胎児期や乳幼児期における環境化学物質曝露が、次世代やさらにそれ以降の世代にまで健康に悪影響を及ぼす可能性が指摘されている。無機ヒ素についても、疫学研究や動物実験により、F1やF2での肝腫瘍発症率の増加が報告されているが、詳細は明らかになっていない。本研究では、F2の肝実質細胞において、脂肪蓄積や糖新生に関与する遺伝子の発現が変化することを明らかにでき、ヒ素による世代を超えた後発影響についてどの細胞がどのような影響を受けるかの実態の理解及びそれに基づく予測・予防に資する基礎的データを得ることができた。
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