Studies on epimutations that are involved in multigenerational effects of environmental chemicals in mice

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293154
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: National Institute for Environmental Studies
• Principal Investigator: Nohara Keiko 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, フェロー (50160271)
• Co-Investigator(Kenkyū-buntansha): 畑田 出穂 群馬大学, 生体調節研究所, 教授 (50212147) ; 秦 健一郎 国立研究開発法人国立成育医療研究センター, 周産期病態研究部, 部長 (60360335)
• Co-Investigator(Renkei-kenkyūsha): Nakabayashi Kazuhiko 国立研究開発法人国立成育医療研究センター, 周産期病態研究部, 室長 (10415557) ; 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) ; Okamura Kazuyuki 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, 研究員 (50736064) ; Horii Takuro 群馬大学, 生体調節研究所, 助教 (00361387) ; Morita Sumiyo 群馬大学, 生体調節研究所, 研究員 (40589264)
• Research Collaborator: Matsushita Junya 東京理科大学, 大学院薬学研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 無機ヒ素 / 妊娠期曝露 / 肝腫瘍 / F2影響 / DNAメチル化 / miRNA

Outline of Final Research Achievements

The F2 pups of C3H mice born to F1 males which are gestationally exposed to arsenic develop liver tumors at higher rates compared to the control mice. We hypothesized that arsenic exposure induces heritable epimutations in the F1 male germ cells and these epimutations cause somatic mutations and tumor increase in the F2 livers. Thus, we analyzed genome-wide DNA methylation status and microRNA composition of the normal and tumor tissues of control and gestationally arsenic-exposed F2 mice by a next generation sequencing-based method and by using microarrays, respectively. We clarified DNA methylation status of normal livers and tumor tissues of C3H mice and identified tumor-associate changes and arsenic exposure-specific changes which correspond to changes in gene expressions. We also identified arsenic exposure-specific expression changes of miRNA whose targets are involved in tumorigenesis. These results shortlisted the candidate genes involved in the F2 effects by arsenic exposure.

Free Research Field

分子毒性学