Selenium modifies the metabolism and toxicity of arsenic in primary rat hepatocytes

Arsenic and selenium are metalloids with similar chemical properties and me tabolic fates. Inorganic arsenic (iAs) has been shown to modify metabolism and toxicity of inorganic and organic selenium compounds. However, little i s known about effects of selenium on metabolism and toxicity of iAs. The pr esent work examines the effects of selenite (Se-IV) on the cellular retenti on, methylation, and cytotoxicity of trivalent iAs, arsenite (iAs(III)), in primary cultures of rat hepatocytes. The concurrent exposure to Se-IV (0.1 to 6 muM) inhibited methylation and/or significantly increased cellular re tention of iAs(III) in cultured cells. The ratio of the methylated metaboli tes produced from iAs(III), dimethylarsenic (DMAs) to methylarsenic (MAs), decreased considerably in cells treated with Se-IV, suggesting that synthes is of DMAs from MAs may be more susceptible to inhibition by Se-IV than is the production of MAs from iAs(III). The 24-h preexposure to 2 muM Se-IV ha d a similar but less pronounced inhibitory effect on the methylation of iAs (III) in cultured cells. The exposure to 2 muM Se-IV alone for up to 24 h h ad no effect on the viability of cultured hepatocytes. However, concurrent exposure to 2 muM Se-IV increased the cytotoxicity of iAs(III) and its mono - and dimethylated metabolites that contain trivalent arsenic, MAsIII and D MAsIII. These data suggest that pre- or coexposure to inorganic selenium ma y enhance the toxic effects of iAs, increasing its retention in tissues and suppressing its methylation, which may be a pathway for detoxification of iAs. (C) 2001 Academic Press.