Epigenetic mechanisms underlying arsenic-induced toxicity

Millions of individuals world-wide are exposed to potentially harmful levels of inorganic arsenic that exceed the World Health Organization (WHO) recommended limit of 10 μg/L. To date, studies on inorganic arsenic-associated epigenetic modifications suggest numerous mechanisms by which inorganic arsenic impacts DNA methylation, miRNA expression, and histones. For example, evidence supports that inorganic arsenic modifies the enzymatic activity of DNA methyltransferases, histone deacetylase (HDAC) and histone acetyltransferase (HAT). Both in vitro and in vivo evidence support that inorganic arsenic acts as an epigenetic modifier of genes involved in critical cellular functions such as cellular growth and immune response. Future research should focus on scientific gaps related to the functional consequences of the epigenetic modifications, the impact of sexual dimorphism of epigenetic marks, the cross-talk among epigenetic modifiers, and the temporal stability of epigenetic marks.