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THE REACTIVE OXYGEN SPECIES (ROS) THEORY OF ARSENIC CARCINOGENESIS
Citation:
Kitchin, K T. AND S Ahmad. THE REACTIVE OXYGEN SPECIES (ROS) THEORY OF ARSENIC CARCINOGENESIS. Presented at 5th International Conference on Arsenic Exposure and Health Effects, San Diego, CA, 07/14-18/2002.
Description:
At this time, there is not a scientific consensus on the mechanisms/modes of action for arsenic carcinogenesis. Proposed mechanisms/modes of action for arsenic carcinogenesis include but are not limited to clastogenic effects, mutation, oxidative stress (via ROS and other chemical species), gene amplification, altered DNA methylation, cell proliferation, promotion of carcinogenesis, effects on the progression stage, inhibition of DNA repair and interaction with important cellular proteins.
Oxidative stress from arsenic exposure might result either (a) from arsenic species such as dimethylarsenic radical and dimethylarsenic peroxy radical, (b) from release of from ferritin (by dimethylarsinous acid (DMA(III) and dimethylarsinic acid (DMA(V))) or from induction of heme oxygenase (by arsenite), (c) from redox cycling of trivalent to pentavalent arsenic forms or (d) from ROS such as superoxide, hydrogen peroxide, hydroxy radical or singlet oxygen. Arsenic carcinogenesis may proceed via hydroxy radical production by the Haber-Weiss reaction.
Various investigators have shown that arsenic exposures increase 8-hydroxy-2'-deoxyguanosine concentrations in mouse urine, rat liver and human skin. Elevations in ROS concentrations can lead to increased 8-hydroxy-2'-deoxyguanosine concentration, single strand breaks in DNA and G-->T mutations in DNA.
Arsenic is a human carcinogen in skin, lung, liver, urinary bladder and kidney. Elucidating the mechanisms/modes of arsenic carcinogenesis would contribute to a more quantitative and scientifically based risk assessment for arsenic, a major world public health problem.
(Disclaimer: This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.)