6. Conclusion

Arsenic, having a high reactivity with cellular contents, can have diverse and deleterious effects on the cells. One of the important players of arsenic-induced toxicity is the generation of ROS, which can lead to DNA damage and lipid peroxidation. Another important effect is the arsenic exposure that causes the depletion of methyl groups in cellular milieu. Hypomethylation of promoter regions can lead to overexpression of genes which play a key role in cell proliferation, differentiation and apoptosis. As mentioned earlier, DNA hypomethylation upregulates receptors like ER-α making the cells more sensitive towards endogenous steroids. Arsenic is reported to activate PKC which activates MAPK pathway leading to the activation of various transcription factors like AP-1. AP-1 is considered as a crucial player in regulation of cell proliferation, differentiation and apoptosis. Arsenic effects extracellular matrix through upregulation of MMPs resulting in degradation of extracellular matrix having consequences in cellular migration, angiogenesis, proliferation and apoptosis. The biological effects of arsenic are so diverse that multiple

mechanisms have been proposed for the toxicity of the arsenic. The mechanisms involved in the arsenic-induced carcinogenesis are also diverse and complicated. DJ-1 is a multifunctional protein that is activated upon cellular stress response. Most of the studies on DJ-1 protein are related to oxidative stress, although implication of its activity in ER stress response has been shown. The interaction of arsenic with sulfhydryl groups in proteins is considered one of the principal mechanisms which triggers the cellular responses. The binding of trivalent arsenicals to thiols in intracellular and cell surface proteins often results in aberrations of normal cellular processes including alteration of cell–cell communication. Cell–cell communication mediated by connexins, especially Cx43, the most commonly expressed connexin in different cell types, is also disrupted by arsenic binding to its highly conserved cysteine residues. In general, the effect of direct binding of arsenic species to enzyme activity cannot be ruled out in toxicity-related investigations, where other factors like the reactive oxygen species are often implicated. New methodologies are needed to analyze the health effects of arsenic and how people cope with the socioeconomic consequences of the disease. Arsenic toxicity being a global phenomenon constitutes a major public health issue, and therefore an intense research is warranted.
