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SELENIUM MODIFIES THE METABOLISM AND TOXICITY OF ARSENIC IN PRIMARY RAT HEPATOCYTES
Styblo, M. AND D J. Thomas. SELENIUM MODIFIES THE METABOLISM AND TOXICITY OF ARSENIC IN PRIMARY RAT HEPATOCYTES. TOXICOLOGY AND APPLIED PHARMACOLOGY 172:52-61.
Selenium Modifies the Metabolism and Toxicity of Arsenic in Primary Rat Hepatocytes. Miroslav Styblo, David J. Thomas (2000) Toxicol. Appl. Pharmacol.
Arsenic and selenium are metalloids with similar chemical properties and metabolic fates. Inorganic arsenic (iAs) has been shown to modify metabolism and toxicity of inorganic and organic selenium compounds. However, little is known about effects of selenium on metabolism and toxicity of iAs. The present work examines the effects of selenite (SeIV) on the cellular retention, methylation, and cytotoxicity of trivalent iAs, arsenite (iAsIII), in primary cultures of rat hepatocytes. Concurrent exposure or 24-hour pre-exposure to SeIV (0.1 to 6 mM) inhibited methylation and/or significantly increased cellular retention of iAsIII in cultured cells. The ratio of the methylated metabolites, dimethylarsenic (DMAs) to methylarsenic (MAs), decreased considerably in cells treated with SeIV, suggesting that synthesis of DMAs from MAs may be more susceptible to inhibition by SeIV than is the production of MAs from iAsIII. The exposure to 2 mM SeIV alone for up to 24 hours had no effect on the viability of cultured hepatocytes. However, concurrent exposure to 2 mM SeIV increased the cytotoxicity of iAsIII and its mono- and dimethylated metabolites that contain trivalent arsenic, MAsIII and DMAsIII. These data suggest that pre- or co-exposure to inorganic selenium may enhance the toxic effects of iAs, increasing its retention in tissues and suppressing its methylation, which may be a pathway for detoxification of iAs.
Key Words: Arsenic, selenium, toxicity, metabolism, methylation, cell culture, rat hepatocytes.