Figure 2

Mechanisms of arsenic-induced carcinogenesis. Carcinogenic effects induced by arsenic exposure are mostly generated due to its biotransformation process, having effects at genetic and epigenetic levels. Arsenic biotransformation occurs through a series of cycles of reduction, oxidation, and methylation reactions. Pentavalent arsenic (As^V) is reduced to arsenite (As^III), using glutathione (GSH) and thioredoxin (TRX) as electron donors. In the excretion process, As^III is methylated using S-Adenosyl methionine (SAM) as a source of methyl groups resulting in generation of arsenic species with higher carcinogenic potential. Genetic alterations are largely due to generation of reactive oxygen and/or nitrogen species, partially derived from arsenic-induced mitochondrial dysfunction. Epigenetic effects, such as changes in DNA methylation patterns have been linked to deprivation of SAM.