Arsenic-Associated Changes to the Epigenome: What Are the Functional Consequences?

Inorganic arsenic (iAs) poses a major threat to worldwide human health, and yet the molecular mechanisms underlying the toxic effects associated with iAs exposure are not well understood. There is increasing experimental evidence indicating that epigenetic modifications may play a major role in the development of diseases associated with exposure to environmental toxicants. Research in the field has firmly established that iAs exposure is associated with epigenetic alterations including changes in DNA methylation, miRNA abundance, and post-translational histone modifications. Here, we summarize recent studies that have expanded the current knowledge of these relationships. These studies have pinpointed specific regions of the genome and genes that are targets of arsenical-induced epigenetic changes, including those associated with iAs exposure. The recent literature indicates that iAs biotransformation likely plays an important role in the relationship between iAs exposure and the epigenome, in addition to the sex and genetic background of individuals. The research also shows that relatively low to moderate exposure to iAs is associated with epigenetic effects. However, while it is well established that arsenicals can alter components of the epigenome, in many cases, the biological significance of these alterations remains unknown. The manner by which these and future studies may help inform the role of epigenetic modifications in the development of iAs-associated disease is evaluated and the need for functional validation emphasized.