Evidence for the involvement of sulfhydryl compounds in the inhibition of cellular DNA synthesis by selenite.

Abstract

Previous studies have demonstrated that selenite inhibits cellular DNA synthesis. We have now found that endogenous cellular sulfhydryl compounds are involved in this effect of selenite. Treatment of cells with diethylmaleate, which produces a nonspecific depletion of cellular sulfhydryl compounds, resulted in a significant decrease in the sensitivity of DNA synthesis to inhibition by selenite. This decrease was eliminated by exogenous cysteine, but not by cystine. Similarly, DNA synthesis in nuclei isolated from diethylmaleate-treated cells was much less sensitive to inhibition by selenite than was synthesis in nuclei isolated from control cells. In contrast, treatment with buthionine sulfoximine, which specifically depletes the cells of glutathione, had no effect on the inhibition of DNA synthesis by selenite, indicating that cellular glutathione is not involved in the inhibition. Nevertheless, glutathione is able to compensate to some extent for the decreased level of sulfhydryl compounds in nuclei isolated from DEM-treated cells (although not as well as cysteine). Thus, although glutathione is able to potentiate the inhibition of cellular DNA synthesis by selenite, it apparently does not function in this capacity in the cell.