Involvement of oxidative stress in the epigenetic changes induced by environmental chemicals

氧化应激与各种环境化学物质的毒性作用有关。本研究旨在探讨氧化应激与DNA甲基化变化之间的联系。喂养缺乏甲基的饮食会诱导小鼠肝脏中氧化应激反应基因和DNA损伤，这表明诱导了氧化应激。缺乏甲基的饮食也减少了DNA甲基化。作为DNA甲基化降低的一个有希望的原因，本研究的结果表明参与活跃的DNA去甲基化途径的基因被诱导，这表明氧化应激诱导了活跃的DNA去甲基化。我们还在gpt Delta转基因小鼠中阐明了亚砷可以诱导G：C到T：A的转换，这种突变可能是通过氧化应激诱导8-OHdG的形成而引起的。这是关于砷的体内致突变性的首次报道。

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.