Cytotoxic effects of hexavalent and trivalent chromium on mammalian cells in vitro.

The cytotoxic effects of hexavalent (k(2)Cr(2)O(7)) and trivalent (CrCl(3)) chromium compounds have been studied in cultured hamster fibroblasts (BHK line) and human epithelial-like cells (HEp line).K(2)Cr(2)O(7) stimulates the uptake of labelled thymidine into the soluble intracellular pool (the stimulation of nucleoside uptake represents a specific effect of Cr(6+)) while Cr(3+) always exerts an inhibitory action. DNA Synthesis is inhibited by treatment with both chromium compounds, but especially by K(2)Cr(2)O(7). Moreover, the effective CrCl(3) concentrations reduce the sensitivity of DNA and RNA to hydrolysis with perchloric acid. Treatments with k(2)Cr(2)O(7) in balanced salt solution, where Cr(6+) reduction is less marked, induce more pronounced cytotoxic effects than treatments in complete growth medium.HEp cells turned out to be more sensitive to K(2)Cr(2)O(7) than BHK fibroblasts: in the former line TdR uptake is less stimulated, DNA synthesis and cell survival are more affected. Survival of BHK cells to K(2)Cr(2)O(7) indicates a multi-hit mechanism of cell inactivation, the extrapolation number being about 10.On the basis of quantitative Cr determinations in the treatment solutions and in the treated cells, the cytotoxic effects of Cr are attributed to the action of Cr(6+) at the plasma membrane level on the mechanisms involved in nucleoside uptake, and to the interaction of Cr(3+) at the intracellular level with nucleophilic targets on the DNA molecule.