ToxStrategies scientists were recently invited to contribute an article to the special issue “Genomic Toxicology: Epigenetics” in Current Opinion in Toxicology. An overview of relationships between chemical-induced changes in epigenetic mechanisms, including histone modifications, DNA methylation, and microRNA expression, and genotoxicity were reviewed and presented. Several examples of chemical carcinogens for which epigenetic alterations and DNA damage have been previously demonstrated were discussed. Examples included: (i) preferential binding of reactive chemicals or metabolites to methylated cytosines at mutational “hotspots” that lead to carcinogenesis, (ii) histone modifications that affect chromatin structure, resulting in altered accessibility of DNA to damaging agents and/or DNA repair machinery and/or recruitment of DNA repair machinery to sites of damage, and (iii) changes in abundance of microRNAs that regulate the expression of genes involved in DNA damage response.
Importantly, there is a general lack of available data demonstrating direct relationships between chemical-induced genetic damage and epigenetic responses (whether deleterious or protective) was identified; this together with the need for research to improve this paucity is highlighted in the review. A better understanding of epigenetic mechanisms involved in chemical carcinogenesis was postulated to advance the application of epigenetics data in hazard assessments of chemicals.
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