Environmental Agents and Epigenetics

Publisher Summary This chapter reviews the evidence that associates epigenetic mechanisms with the toxic and carcinogenic effects of certain environmental agents. Many of these chemicals have been shown to modify the same or similar epigenetic marks found in patients with disease states associated with that agent. For example, the increase in global DNA hypomethylation levels and promoter specific hypermethylation of tumor suppressor genes in response to arsenic exposure is consistent with the observed promoter specific hypermethylation and widespread loss in DNA methylation levels exhibited by cancer cells. Exposure to environmental factors such as metals, the semi-metal selenium, peroxisome proliferators, radiation, particulate matter, tobacco smoke, benzene, endocrine disruptors, and polycyclic aromatic hydrocarbons, perturb global and gene-specific DNA methylation levels as well as histone posttranslational modifications. Although the mechanism(s) by which these chemicals perturb the epigenome is unknown, many studies suggest an alteration in the expression and/or activity of enzymes that modify DNA and histone tails such as DNA methyltransferases and histone methyltransferases, deacetylases, and demethylases. Therefore, the evidence emphasizes the importance of applying to toxicological research the understanding that genotoxic mechanisms are not the sole mechanism underlying the changes in gene expression leading to cancer and other disease states.