Superfund Research Program
Nutritional Influences on Blood Arsenic, Arsenic Methylation and Cognitive Function in Children
Final Progress Reports
The carcinogenic mechanisms of aresenic are incompletely understood, but emerging evidence suggests that arsenic exposure leads to dysregulation of epigenetic process that can influence gene expression and genomic stability. In a Bangladesh cohort researchers demonstrated that chronic arsenic exposure is associated with increased global DNA methylation, contingent on adequate folate status. It is hypothesized that the mechanism underlying this relates to arsenic-induced alterations in histone modifications.
Folate is a key regulator of one-carbon metabolism mediated methylation reactions, including epigenetic modifications such as methylation of DNA and histones. A large randomized trial in Bangladesh has evaluated the effects of folic acid (FA) supplementation on arsenic methylation and blood arsenic concentrations. The research team conducted a cross-disciplinary collaboration using samples collected from this trial to carry out a set of aims related to nutrition/environment interactions. In these aims, researchers characterized the influence of arsenic exposure on histone modifications, changes in DNA methylation, and the impact of FA supplementation on these marks (Howe 2016). Finally, a set of genes that are differentially methylated and/or expressed by arsenic exposure was identified. These aims have begun to elucidate the molecular events that underlie the effects of arsenic and folate on DNA methylation. The implications of identifying an influence of FA supplementation on histone modifications and DNA methylation are considerable, as this represents a simple, low-cost, low-risk intervention as a potential therapeutic approach to reverse arsenic-induced epigenetic dysregulation.