Epigenomic Analysis in Toxicology

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI:10.1002/9780470744307.GAT230

T. Ushijima, E. Okochi‐Takada, Hideyuki Takeshima

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Abstract

Epigenetic modifications are essential for development, differentiation, and reprogramming. They are inherited upon somatic cell replication, and include DNA methylation and histone modifications. Abnormality of epigenetic modifications is deeply involved in human cancers, as known by global hypomethylation and regional hypermethylation. Recent findings on the high fraction of cells affected in normal-appearing tissues indicated that epigenomic alterations are also involved in acquired disorders other than cancers. In spite of the deep involvement of epigenomic alterations in human diseases, only limited information is available for inducers of epigenetic changes, including aging, chronic inflammation, virus infection, disturbances in one carbon metabolism, and some chemicals. One of the reasons why a very limited number of chemicals are known as inducers of epigenetic alterations (epimutagens) is the lack of a sufficiently convenient and sensitive assay system. Toxicological considerations from the viewpoint of epigenomics are critically important, and epigenomic toxicology has just started. Keywords: epigenetics; DNA methylation; histone modification; epigenome; cancer; epimutation; epimutagen

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毒理学中的表观基因组分析

表观遗传修饰对发育、分化和重编程至关重要。它们在体细胞复制时遗传，包括DNA甲基化和组蛋白修饰。表观遗传修饰的异常与人类癌症密切相关，如全球低甲基化和区域高甲基化。最近对正常组织中受影响细胞的高比例的研究表明，表观基因组改变也涉及除癌症以外的获得性疾病。尽管表观基因组改变在人类疾病中有着深刻的作用，但对于表观遗传变化的诱导因子，包括衰老、慢性炎症、病毒感染、一种碳代谢紊乱和一些化学物质，仅有有限的信息可获得。很少几种化学物质被称为表观遗传改变诱导剂(表观诱导剂)的原因之一是缺乏足够方便和敏感的分析系统。从表观基因组学的角度考虑毒理学问题是至关重要的，而表观基因组毒理学才刚刚起步。关键词:表观遗传学;DNA甲基化;组蛋白修饰;表观基因组;癌症;epimutation;epimutagen

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General, Applied and Systems Toxicology

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