Project/Area Number |
23390166
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hygiene
|
Research Institution | National Institute for Environmental Studies |
Principal Investigator |
NOHARA Keiko 独立行政法人国立環境研究所, 環境健康研究センター, 室長 (50160271)
|
Co-Investigator(Kenkyū-buntansha) |
SANO Tomoharu 独立行政法人国立環境研究所, 環境計測研究センター, 主任研究員 (10178808)
AOKI Yasunobu 独立行政法人国立環境研究所, 環境リスク研究センター, センター長 (20159297)
|
Co-Investigator(Renkei-kenkyūsha) |
TAKUMI Shota 独立行政法人国立環境研究所, 環境健康研究センター, 特別研究員 (80570770)
|
Research Collaborator |
NOHMI Takehiko 独立行政法人医薬基盤研究所, 創薬支援戦略室, コーディネーター (30150890)
OKAMURA Kazuyuki 筑波大学, 大学院・持続環境学専攻, 大学院生
SUZUKI Takehiro 独立行政法人国立環境研究所, 環境健康研究センター, 主任研究員 (60425494)
|
Project Period (FY) |
2011-04-01 – 2014-03-31
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
|
Keywords | 酸化ストレス / エピジェネティクス / DNAメチル化 / メチル欠乏食 / 無機ヒ素 / 突然変異 / 能動的脱メチル化 / 5メチルシトシン / 5ヒドロキシメチルシトシン / 能動的DNA脱メチル化 / 低メチル食 / 酸化的DNA損傷 / グローバルDNAメチル化量 / Tet酵素 / DNA損傷修復酵素 / 5-メチルシトシン / DNAメチル基転移酵素 |
Research Abstract |
Oxidative stress is implicated in the toxic effects of various environmental chemicals. This study aimed to explore the linkage between oxidative stress and DNA methylation changes. Feeding a methyl-deficient diet induced oxidative stress-responsive genes and DNA damage in the mouse liver, indicating induction of oxidative stress. The methyl-deficient diet also reduced DNA methylation. As a promising causation of the lowered DNA methylation, the results of this study indicated the induction of genes involved in the active DNA demethylation pathways, suggesting induction of the active DNA demethylation by oxidative stress. We also clarified in the gpt delta transgenic mice that arsenite induces G:C to T:A transversions and the mutation is suggested to be caused through oxidative-stress-induced 8-OHdG formation. This is the first report on in vivo mutagenecity of arsenic in vivo.
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