THE SELENIUM METABOLITE SELENODIGLUTATHIONE INDUCES CELL-DEATH BY A MECHANISM DISTINCT FROM H2O2 TOXICITY

Our previous studies have implicated the selenium metabolite selenodiglutathione (SDG) in the growth inhibitory effects of selenite lit vitro. Other work has suggested that reactive oxygen species, the superoxide anion and hydrogen peroxide, may be implicated in selenite toxicity, In this study the mechanism of growth inhibition by SDG and H2O2 has been compared in a mammary cell line, C57. Both SDG and H2O2 had a rapid effect on C57 cells and markedly reduced cloning efficiency within 1 h. However, the mechanisms involved seem to be different, as judged by the following observations: (i) An SDG-resistant cell line (B19) derived from C57 cells is cross-resistant to selenite, but not H2O2; (ii) SDG reduces the levels of the mRNAs for phospholipid hydroperoxide glutathione peroxidase and cytosolic glutathione peroxidase, whereas H2O2 has no effect; (iii) SDG induces both 560 kb and 50 kb DNA fragments, whereas H2O2 only induces 560 kb DNA fragments. This is of interest, since formation of high molecular weight DNA fragments has been recognized as a characteristic of apoptosis.