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Tom Hei Background: Arsenic is a metalloid element present throughout the earth's crust. Although history and fiction are peppered with references to the acute toxicity and lethality of arsenic, its carcinogenic potential is not as well known. Long-term exposure to arsenic can occur by consumption of contaminated drinking water and food, and through arsenical drugs. Inhalation exposure can also occur from ore smelting, semiconductor and glass manufacturing, and the burning of arsenic containing coal. Chronic arsenic exposure has been shown to cause liver injury, peripheral neuropathy, and cancer of the skin, bladder, liver, and lungs. Arsenic contamination of drinking water is a serious problem worldwide based on the lack of safe drinking water in some areas and the number of people at risk. Arsenic carcinogenicity is a perplexing problem in that it is one of a few, if not the only known human carcinogen that does not cause cancer in laboratory animal models. Therefore, the mechanism by which it causes cancer is poorly understood. Advance: Previous work by this investigator has shown that the trivalent form of arsenic, arsenite, causes oxidative damage leading to genotoxic effects. This paper demonstrates that arsenite increases the levels of superoxide-driven hydroxyl radicals in a cell culture model. Additionally, removing glutathione, which protencts cells from free radical damage, increases the mutagenic potential of arsenite 5-fold. Implication: These data provide further evidence that free radicals or reactive oxygen species, particularly hydroxyl radicals, produced in response to arsenite exposure, play an important role in the carcinogenic mechanism of arsenic compounds. Also, free radical scavengers such as glutathione play a protective role by reducing hydroxyl radical concentrations. Citation: Liu SX, Athar M, Lippai I, Waldren C, Hei TK. Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1643-8. |
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