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环境毒物、表观遗传学与癌症。

Environmental toxicants, epigenetics, and cancer.

机构信息

Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.

出版信息

Adv Exp Med Biol. 2013;754:215-32. doi: 10.1007/978-1-4419-9967-2_11.

Abstract

Tumorigenesis, a complex and multifactorial progressive process of transformation of normal cells into malignant cells, is characterized by the accumulation of multiple cancer-specific heritable phenotypes triggered by the mutational and/or non-mutational (i.e., epigenetic) events. Accumulating evidence suggests that environmental and occupational exposures to natural substances, as well as man-made chemical and physical agents, play a causative role in human cancer. In a broad sense, carcinogenesis may be induced through either genotoxic or non-genotoxic mechanisms; however, both genotoxic and non-genotoxic carcinogens also cause prominent epigenetic changes. This review presents current evidence of the epigenetic alterations induced by various chemical carcinogens, including arsenic, 1,3-butadine, and pharmaceutical and biological agents, and highlights the potential for epigenetic changes to serve as markers for carcinogen exposure and cancer risk assessment.

摘要

肿瘤发生是一个复杂的、多因素的正常细胞向恶性细胞转化的渐进过程,其特征是多种癌症特异性遗传表型的积累,这些表型是由突变和/或非突变(即表观遗传)事件触发的。越来越多的证据表明,环境和职业暴露于天然物质以及人为的化学和物理因素在人类癌症中起致病作用。广义上讲,致癌作用可能通过遗传毒性或非遗传毒性机制诱导;然而,遗传毒性和非遗传毒性致癌物也会引起明显的表观遗传变化。本综述介绍了各种化学致癌物(包括砷、1,3-丁二烯以及药物和生物制剂)诱导的表观遗传改变的最新证据,并强调了表观遗传改变作为致癌物暴露和癌症风险评估标志物的潜力。

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