Environmental chemical stressors as epigenome modifiers:a new horizon in assessment of toxicological effects  

作　　者：Heqing Shen F.L.Martin Yanhua Su 

机构地区：[1]Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences [2]Centre for Biophotonics, Lancaster Environment Centre,Lancaster University [3]Department of Preventive Medicine, School of Public Health of Xiamen University

出　　处：《Chinese Science Bulletin》2014年第4期349-355,共7页

基　　金：supported by Hundred Talent Program of Chinese Academy of Sciences for 2010 on Human Exposure to Environmental Pollutant and Health Effect,National Natural Science Foundation of China(21177123);Xiamen Science and Technology Fund(3502Z20122003)

摘　　要：In eukaryotic cells, chromatin transformation from euchromatin into heterochromatin as a means of controlling gene expression and replication has been known as the ‘‘accessibility hypothesis' '. The interplay of epigenetic changes including histone modifications, DNA methylation, RNA interference(RNAi) and other func- tional epigenetic components are intricate. It is believed that these changes are well-programmed, inherited and can be modified by environmental contaminant stressors. Environmentally-driven epigenetic alterations during development, e.g. embryonic, foetal or neonatal stage, may influence disease susceptibility in adulthood. Therefore, understanding how epigenome modifications develop in response to environmental chemicals and, how epigenetic-xenobiotic interactions influence human health will shed new insights into gene-environment interactions in the epidemiology of several diseases including cancer. In this review, we consider studies of chemical modifiers including nutritional and xenobiotic effects on epigenetic components in vitro or in vivo. By examining the most-studied epigenome modifications and how their respective roles are interlinked, we highlight the central role of xenbiotic- modified epigenetic mechanisms. A major requirement will be to study and understand effects following environmentally-relevant exposures. We suggest that the study of epigenetic toxicology will open up new opportunities to devise strategies for the prevention or treatment of at-risk populations.In eukaryotic cells, chromatin transformation from euchromatin into heterochromatin as a means of controlling gene expression and replication has been known as the ＂accessibility hypothesis＂. The interplay of epigenetic changes including histone modifications, DNA methylation, RNA interference （RNAi） and other func- tional epigenetic components are intricate. It is believed that these changes are well-programmed, inherited and can be modified by environmental contaminant stressors. Environmentally-driven epigenetic alterations during development, e.g. embryonic, foetal or neonatal stage, may influence disease susceptibility in adulthood. Therefore, understanding how epigenome modifications develop in response to environmental chemicals and, how epigenetic- xenobiotic interactions influence human health will shed new insights into gene-environment interactions in the epidemiology of several diseases including cancer. In this review, we consider studies of chemical modifiers includ- ing nutritional and xenobiotic effects on epigenetic com- ponents in vitro or in vivo. By examining the most-studied epigenome modifications and how their respective roles are interlinked, we highlight the central role of xenbiotic- modified epigenetic mechanisms. A major requirement will be to study and understand effects following environmen- tally-relevant exposures. We suggest that the study of epigenetic toxicology will open up new opportunities to devise strategies for the prevention or treatment of at-risk populations.

关 键 词：环境化学 基因修饰 压力源 表观 毒理效应 评估 DNA甲基化 相互作用 

分 类 号：X171.5[环境科学与工程—环境科学]