Epimutagenesis: A prospective mechanism to remediate arsenic-induced toxicity

Abstract

Arsenic toxicity is a global issue, addressed by the World Health Organization as one of the major natural calamities faced by humans. More than 137 million individuals in 70 nations are affected by arsenic mainly through drinking water and also through diet. Chronic arsenic exposure leads to various types of patho-physiological end points in humans including cancers. Arsenic, a xenobiotic substance, is biotransformed in the body to its methylated species by using the physiological S-adenosyl methionine (SAM). SAM dictates methylation status of the genome and arsenic metabolism leads to depletion of SAM leading to an epigenetic disequilibrium. Since epigenetics is one of the major phenomenon at the interface between the environment and human health impact, its disequilibrium by arsenic inflicts upon the chromatin compaction, gene expression, genomic stability and a host of biomolecular interactions, the interactome within the cell. Since arsenic is not mutagenic but is carcinogenic in nature, arsenic induced epimutagenesis has come to the forefront since it determines the transcriptional and genomic integrity of the cell. Arsenic toxicity brings forth several pathophysiological manifestations like dermatological non-cancerous, pre-cancerous and cancerous lesions, peripheral neuropathy, DNA damage, respiratory disorders and cancers of several internal organs. Recently, several diseases of similar manifestations have been explained with the relevant epigenetic perspectives regarding the possible molecular mechanism for their onset. Hence, in the current review, we comprehensively try to intercalate the information on arsenic-induced epigenetic alterations of DNA, histones and microRNA so as to understand whether the arsenic-induced toxic manifestations are brought about by the epigenetic changes. We highlight the need to understand the aspect of epimutagenesis and subsequent alterations in the cellular interactome due to arsenic-induced molecular changes, which may be utilized to develop putative therapeutic strategies targeting both oxidative potential and epimutagenesis in humans.

Keywords: Arsenic; DNA methylation; Epimutagenesis; Histone post-translational modifications; Human health; miRNA.