Cellular uptake, cytotoxic and mutagenic effects of insoluble chromic oxide in V79 Chinese hamster cells

Abstract

The cellular uptake, the cytotoxicity and the induction of resistance to 6-thioguanine (6-TG) in Chinese hamster V79 cells exposed to insoluble crystalline trivalent chromium [Cr(III)], Cr2O3, were investigated. Intracytoplasmic Cr2O3 crystalline particle-containing vacuoles were observed by electron microscopy. Concentrations of 50-200 micrograms/ml did not have a marked killing effect but did show a predominantly concentration-dependent inhibitory effect on cell cycle progression with accumulation of cells in G2 phase. Exposure for 18 h to Cr2O3 induced a statistically significant (p less than 0.001) increase in the mutation frequency of up to 10-fold over the controls. Expression time was 6 days for the lowest concentration and 9 days for the highest. Culture of 6-TGr clones in selective media indicated that they were mutants at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus. Examination of growth patterns of Cr2O3-induced mutants showed that, after a delay in reinitiating cell growth, they had varying growth kinetics. The results indicate the ability of a particulate (Cr(III) compound to induce mutation in a mammalian cell system and the usefulness of such systems for detecting genotoxic insoluble metal compounds.