CARCINOGENIC CHROMIUM(VI) INDUCES OXIDATIVE STRESS IN CULTURED HUMAN LEUKEMIC T-LYMPHOCYTES. 1. GENERATIO OF HYDROGEN PEROXIDE DURIN INTRACELLULAR REDUCTION OF CHROMATE

Treatment of human leukemic T-lymphocyte MOLT4 cells with potassium chromate, a chromium (VI) compound, increased the form ation of the oxidized compound dichlorofluorescein (DCF), a highly fluorescent compound, from the parent nonfluorescent compound, 2,7-dichlorofluorescin diacetate (DCF-DA). No such increase in DCF formation was observed when cells were treated with Cr(III) compounds. In cell-free system s, dichlorofluorescin diacetate was also oxidized to DCF by strong oxidants (such as hydrogen peroxide and hydroperoxides) in the presence of peroxidase, suggesting that Cr(VI) treatment increased the intracellular level of these peroxides in MOLT4 cells. The rate of generation of peroxides was found to be both dose and time dependent. These results suggest that accumulation of intracellular peroxides may, at least in part, be associated with chromium-induced genotoxicity and add to the emerging concept that these phenomena may, in part, be mediated via oxidative m echanisms.