Cytotoxic Effects of Hexavalent and Trivalent Chromium on Mammalian Cells In Vitro

Abstract

The cytotoxic effects of hexavalent (k₂Cr₂O₇) and trivalent (CrCl₃) chromium compounds have been studied in cultured hamster fibroblasts (BHK line) and human epithelial-like cells (HEp line). K₂Cr₂O₇ stimulates the uptake of labelled thymidine into the soluble intracellular pool (the stimulation of nucleoside uptake represents a specific effect of Cr⁶⁺) while Cr³⁺ always exerts an inhibitory action. DNA Synthesis is inhibited by treatment with both chromium compounds, but especially by K₂Cr₂O₇. Moreover, the effective CrCl₃ concentrations reduce the sensitivity of DNA and RNA to hydrolysis with perchloric acid. Treatments with k₂Cr₂O₇ in balanced salt solution, where Cr⁶⁺ reduction is less marked, induce more pronounced cytotoxic effects than treatments in complete growth medium. HEp cells turned out to be more sensitive to K₂Cr₂O₇ 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 K₂Cr₂O₇ 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 Cr₆₊ at the plasma membrane level on the mechanisms involved in nucleoside uptake, and to the interaction of Cr³⁺ at the intracellular level with nucleophilic targets on the DNA molecule.