Adverse effects of arsenic exposure on DNA methylation:a review of recent studies

Arsenic pollution is a global environment problem. Increasing evidences indicated that the exposure to arsenic is associated with many diseases and with the onset and progressing of tumors. However, the molecular mechanism of arsenic toxicity still remains in debate. Alteration of DNA methylation is one of most important etiologies of arsenic exposure. In vivo and in vitro experiments, and epidemiological investigations showed arsenic induced the alterations of global DNA methylation, but the reported change trend(increase or decrease) derived from these papers are inconsistent. Besides whole genome DNA methylation, the exposure to arsenic changed the methylation status of tumor related gene promoter.The exact mechanism underlying arsenic-induced DNA epigenetic alteration is highly complicated. There are three possible mechanisms, including methyl coupling mechanism with SAM which as a methyl donor, DNMTs and TETs gene disregulation,and disrupted hydroxymethylation process via tricarboxylic acid cycle. These mechanisms interact with each other, consequently result in the disturbance of dynamic DNA epigenetic balance.Although the exact molecular mechanism of DNA epigenetic alteration remains uncompletely clear, these studies provide a bright insight in the research of arsenic toxicity.In this paper, in vitro, in vivo and epidemiological research findings on arsenic-associated DNA epigenetic alteration of global genome and specific genes were briefly summarized, as well as its potential toxicological mechanism.