The present view of arsenic carcinogenesis is that there are many possible chemical forms of arsenic that may be causal in carcinogenesis. In addition, arsenic induced carcinogenesis may have different mechanisms in different tissues with contributions from all species present in that tissue [ROM 2007]. Some studies in arsenic metabolism suggest that methylation of inorganic arsenic may be a toxification, rather than a detoxification pathway and that trivalent methylated arsenic metabolites, particularly monomethylarsonous acid and dimethylarsinous acid, have a great deal of biological activity [Kitchin 2001]. The evidence indicates that trivalent, methylated, and relatively less ionizable arsenic metabolites may be capable of interacting with cellular targets such as proteins and even DNA [Kitchin 2001].
A scientific consensus has not yet been reached on the many suggested modes of arsenic carcinogenesis that exist in the literature. These include modes that are predominately genotoxic (i.e., chromosomal abnormalities, oxidative stress, and gene amplification) vs. more nongenotoxic (i.e., altered growth factors, enhanced cell proliferation and promotion of carcinogenesis, and altered DNA repair). Likewise, the dose-response relationship at low arsenic concentrations for any of these suggested modes is not known [Kitchin 2001].
