Figure 2

Arsenic biotransformation drives carcinogenesis. Arsenic biotransformation occurs through a series 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 of this compound, As^III is methylated using S-Adenosyl methionine (SAM) as a source of methyl groups; however, this result in generation of arsenic species with higher carcinogenic potential[58–62]. Carcinogenic effects are mostly generated due to this biotransformation process, having effects at genetic and epigenetic levels. Genetic alterations are largely due to generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), partially derived from arsenic-induced mitochondrial dysfunction. Epigenetic effects, such as changes in DNA methylation patterns have been linked to deprivation of SAM. Changes in miRNA expression and histone modifications have also been reported.