摘要
砷污染是全球性的问题,砷暴露与多种疾病密切相关,并能诱发癌症。细胞实验、动物模型实验和流行病学研究表明,砷暴露会影响全基因组DNA甲基化水平;另外,砷暴露也被证实会导致原癌基因和抑癌基因等多种基因启动子的甲基化异常。砷暴露干扰DNA甲基化的作用机制非常复杂。砷可能通过砷甲基化与DNA甲基化过程的耦合改变DNA甲基化状态,也可能通过调节DNA甲基化转移酶(DNMTs)的活力或通过氧化应激效应干扰DNA去甲基化来影响DNA甲基化状态。虽然最终的作用机制尚不明确,但是目前的DNA表观基因毒理学研究为砷暴露的环境健康研究提供了新视角。该文就砷对全基因组和特定基因启动子甲基化的影响及其分子作用机制进行综述。
Arsenic pollution is a global environment problem. Increasing evidences indicated that the exposure to arsenic is associated with many diseases and with the onset and progressing of tumors. However, the molecular mechanism of arsenic toxicity still remains in debate. Alteration of DNA methylation is one of most important etiologies of arsenic exposure. In vivo and in vitro experiments, and epidemiological investigations showed arsenic induced the alterations of global DNA methylation, but the reported change trend （increase or decrease） derived from these papers are inconsistent. Besides whole genome DNA methylation, the exposure to arsenic changed the methylation status of tumor related gene promoter.The exact mechanism underlying arsenic-induced DNA epigenetic alteration is highly complicated. There are three possible mechanisms, including methyl coupling mechanism with SAM which as a methyl donor, DNMTs and TETs gene disregulation,and disrupted hydroxymethylation process via tricarboxylic acid cycle. These mechanisms interact with each other, consequently result in the disturbance of dynamic DNA epigenetic balance.Although the exact molecular mechanism of DNA epigenetic alteration remains uneompletely clear, these studies provide a bright insight in the research of arsenic toxicity.In this paper, in vitro, in vivo and epidemiological research findings on arsenic-associated DNA epigenetic alteration of global genome and specific genes were briefly summarized, as well as its potential toxicological mechanism.
出处
《环境与健康杂志》
CAS
CSCD
北大核心
2014年第3期269-276,共8页
Journal of Environment and Health
基金
国家自然科学基金(21177123)
