Selenium prevents spontaneous and arsenite-induced mutagenesis

Abstract

Selenium (Se) and arsenic are next-door neighbors on the periodic table and have similar chemical properties as metalloids. Arsenic antagonizes selenium toxicity in a number of organisms. Inorganic arsenic in drinking water is a human carcinogen while selenium compounds are anticarcinogenic in animals and humans. Our previous work showed that arsenite enhanced solar UV-induced skin cancer in the hairless mouse and caused delayed mutagenesis in human HOS cells. Here, we assess the abilities of three selenium compounds to antagonize arsenite. Sodium selenite is far more toxic to HOS cells than selenomethionine and Se-(methyl)selenocysteine in a 10-day clonality assay. When concentrations subtoxic in the clonality assay were assessed for long-term effects on growth, selenite, but not the organic compounds, caused a delayed inhibitory effect after 3 weeks. None of the Se compounds effectively blocked arsenite toxicity. Both organoselenium compounds blocked spontaneous and arsenite-induced delayed mutagenesis. The mechanism of delayed mutagenesis by arsenite is not known, but reactive oxygen species may play a role. We suggest that the antimutagenic action of organoselenium might result from up-regulation of the selenoproteins GSH peroxidase and thioredoxin reductase, which would protect against spontaneous and arsenite-induced oxidative DNA damage.