Smirnova Lena, Sittka Alexandra, Luch Andreas
Department of Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.
Exp Suppl. 2012;101:499-550. doi: 10.1007/978-3-7643-8340-4_18.
For a long time, scientists considered genotoxic effects as the major issue concerning the influence of environmental chemicals on human health. Over the last decades, a new layer superimposed the genome, i.e., the epigenome, tremendously changing this point of view. The term "epigenetics" comprises stable alterations in gene expression potential arising from variations in DNA methylation and a variety of histone modifications, without changing the underlying DNA sequence. Recently, also gene silencing by small noncoding RNAs (ncRNAs), in particular by microRNAs, was included in the list of epigenetic mechanisms. Multiple studies in vivo as well as in vitro have shown that a multitude of different environmental factors are capable of changing the epigenetic pattern as well as miRNA expression in certain cell types, leading to aberrant gene expression profiles in cells and tissues. These changes may have extensive effects concerning the proper gene expression necessary in a specified cell type and can even lead into a state of disease. Especially the roles of epigenetic modifications and miRNA alterations in tumorigenesis have been a major focus in research over the last years. This chapter will give an overview on epigenetic features and on the spectrum of epigenetic changes observed after exposure against environmental chemicals and pollutants.
长期以来，科学家们一直认为基因毒性效应是环境化学物质对人类健康影响的主要问题。在过去几十年里，基因组之上叠加了一个新的层面，即表观基因组，这极大地改变了这种观点。“表观遗传学”一词包括由DNA甲基化变化和多种组蛋白修饰引起的基因表达潜能的稳定改变，而不改变潜在的DNA序列。最近，小非编码RNA（ncRNA），特别是微小RNA引起的基因沉默也被列入表观遗传机制列表中。体内和体外的多项研究表明，多种不同的环境因素能够改变某些细胞类型中的表观遗传模式以及miRNA表达，导致细胞和组织中异常的基因表达谱。这些变化可能对特定细胞类型中正常基因表达产生广泛影响，甚至可能导致疾病状态。特别是表观遗传修饰和miRNA改变在肿瘤发生中的作用在过去几年一直是研究的主要焦点。本章将概述表观遗传特征以及接触环境化学物质和污染物后观察到的表观遗传变化范围。
