Szyf Moshe
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montréal, Québec H3G 1Y6, Canada.
Toxicol Sci. 2007 Nov;100(1):7-23. doi: 10.1093/toxsci/kfm177. Epub 2007 Aug 3.
The epigenome serves as an interface between the dynamic environment and the inherited static genome. The epigenome is comprised of chromatin and a covalent modification of DNA by methylation. The epigenome is sculpted during development to shape the diversity of gene expression programs in the different cell types of the organism by a highly organized process. Epigenetic aberrations have similar consequences to genetic polymorphisms resulting in variations in gene function. Recent data suggest that the epigenome is dynamic and is therefore responsive to environmental signals not only during the critical periods in development but also later in life as well. It is postulated here that not only chemicals but also exposure to social behavior, such as maternal care, could affect the epigenome. It is proposed that exposures to different environmental agents could lead to interindividual phenotypic diversity as well as differential susceptibility to disease and behavioral pathologies. Interindividual differences in the epigenetic state could also affect susceptibility to xenobiotics. Although our current understanding of how epigenetic mechanisms impact on the toxic action of xenobiotics is very limited, it is anticipated that in the future, epigenetics will be incorporated in the assessment of the safety of chemicals.
表观基因组充当动态环境与遗传静态基因组之间的接口。表观基因组由染色质和DNA甲基化的共价修饰组成。在发育过程中，表观基因组通过高度有序的过程进行塑造，以形成生物体不同细胞类型中基因表达程序的多样性。表观遗传畸变与基因多态性具有相似的后果，导致基因功能的变化。最近的数据表明，表观基因组是动态的，因此不仅在发育的关键时期，而且在生命后期也对环境信号有反应。本文推测，不仅化学物质，而且接触社会行为，如母性关怀，都可能影响表观基因组。有人提出，接触不同的环境因素可能导致个体间的表型多样性以及对疾病和行为病理学的易感性差异。表观遗传状态的个体差异也可能影响对外源化学物质的易感性。尽管我们目前对表观遗传机制如何影响外源化学物质的毒性作用的理解非常有限，但预计未来表观遗传学将被纳入化学物质安全性评估中。
