Epigenetics in Arsenic Toxicity: Mechanistic Response, Alterations, and Regulations

The widespread toxic metalloid arsenic (As) has the ability to induce oxidative stress through generation of excess reactive oxygen species (ROS) and mediate response of disease states in animals and growth as well developmental traits in plant species through modulation of key cellular signalling molecules and pathways. In recent years, growing evidences are indicating that apart from nucleus-controlled gene expressions, various epigenetic mechanisms play major roles in response, regulations, and alterations of cellular As toxicity. Epigenetic events govern heritable changes that do not involve changes in the nuclear DNA sequence and thus, it is a potentially reversible DNA alteration and a priming mechanism for transgenerational and next generation fitness to better tolerate environmental stresses. As can modulate DNA methylation, the covalent, posttranslational modifications of histone proteins, and small noncoding RNAs or micro-RNA (miRNA) and regulate number of homeostatic and inducible gene expressions. DNA methylation is the most diverse and versatile epigenetic mechanisms of As-induced toxicity in both plants and animals and involves both hypomethylation and hypermethylation in structural gene sequence and promoter regions. On the other hand, As-induced methylation, acetylation, and phosphorylation of histone proteins are some of the prominent events during epigenetic response of As toxicity. Changes in miRNA expressions during As exposure are manifested differential expressions of their target genes and consequent changes in different growth and developmental processes in plants and animal as well as in human system. The complicated interactions among these epigenetic events and capability of As to inherit the epigenetic response mitotically and/or meiotically in next generations and even during foetal programming are some of the interesting events occurred during As-mediated epigenetic response of cell. Also, changes in epigenetic landscape during As-induced processes leading to tumorigenesis and/or carcinogenesis are important cellular events which need to be holistically explored. With development of functional epigenomics, toxicokinetics and rapid advancement of high end precision technologies, As-induced epigenetic footprint or memory may be utilized as a reliable biomarker of future risk assessment for As toxicity.