Cellular uptake, cytotoxic and mutagenic effects of insoluble chromic oxide in V79 Chinese hamster cells.
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.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002857:Chromium / Q000378:metabolism / Q000494:pharmacology*; D017608:Chromium Compounds; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000648:ultrastructure; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008168:Lung; D008297:Male; D009152:Mutagenicity Tests; D010587:Phagocytosis; D012995:Solubility
D017608:Chromium Compounds; D002857:Chromium; C023600:chromic oxide