Metabolism and toxicity of arsenic: A human carcinogen [Review]

摘要

Inorganic arsenic is considered the most potential human carcinogen, and humans are exposed to it from soil, water, air and food. In the process of arsenic metabolism, inorganic arsenic is methylated to monomethylarsonic acid and finally to dimethyl-arsinic acid, followed by excretion through urine. Thus, arsenic exposure may cause DNA hypomethylation due to continuous methyl depletion, facilitating aberrant gene expression that results in carcinogenesis. Further, though arsenic is nonmutagenic, it interacts synergistically with genotoxic agents in the production of mutations, and also induces chromosome abnormalities and cell proliferation. Few epidemiological investigations in the arsenic endemic regions of West Bengal (India) have established that inorganic arsenicals have the potential to cause skin and lung cancers in humans. Studies on the genetic polymorphism in the arsenic methyltransferase(s) with the population exposed to arsenic, and characterization in the arsenic-induced mutational spectra may be useful for the development of molecular markers and therapeutics and for furthering the knowledge of arsenic-induced carcinogenesis.