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砷对 DNA 甲基化影响的研究进展
  • ISSN号:1001-5914
  • 期刊名称:《环境与健康杂志》
  • 时间:0
  • 分类:R994.6[医药卫生—毒理学;医药卫生—药学]
  • 作者机构:[1]中国科学院城市环境研究所城市环境与健康重点实验室,福建厦门361021
  • 相关基金:国家自然科学基金(21177123)
中文摘要:

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。

英文摘要:

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.

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期刊信息
  • 《环境与健康杂志》
  • 中国科技核心期刊
  • 主管单位:国家卫生和计划生育委员会
  • 主办单位:天津市疾病防控制中心 中华预防医学会
  • 主编:王撷秀
  • 地址:天津市河东区华越道6号
  • 邮编:300011
  • 邮箱:hjyjk@263.net
  • 电话:022-24333577
  • 国际标准刊号:ISSN:1001-5914
  • 国内统一刊号:ISSN:12-1095/R
  • 邮发代号:6-221
  • 获奖情况:
  • 中华预防医学会系列杂志优秀期刊,天津市一级期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,美国剑桥科学文摘,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:20716