Comparison of DNA lesions and cytotoxicity induced by calcium chromate in human, mouse, and hamster cell lines.

DNA lesions, cytotoxicity, and cellular uptake of CaCrO4 were compared in Chinese hamster ovary, in mouse embryo fibroblast C3H10T1/2, and in human osteosarcoma cells. The concentration of CaCrO4 that reduced colony formation by 50% was 2- or 3-fold less in human osteosarcoma cells than in C3H10T1/2 or Chinese hamster ovary cells. Alkaline elution studies showed that CaCrO4 induced DNA single strand breaks in a concentration dependent manner in all three cell lines. However, the human cells exhibited four times more breaks than the hamster cells and two times more than C3H10T1/2 cells when the CaCrO4 exposure conditions were equivalent. Alkaline elution studies also demonstrated the formation of DNA-protein cross-links by CaCrO4 in all three cell lines. In hamster and mouse cells the induction of these DNA-protein cross-links was dependent on concentrations that ranged from 5 to 50 microM for 6 h; however, the cross-links were saturated at 25 microM in human cells and at 50 microM in mouse and hamster cells. The level of cross-links was four times greater in the human cells compared to the mouse cells and was a factor of 2 greater in the hamster cells compared to the mouse cells. The uptake of CaCrO4 was linear with respect to time and concentration. Uptake of CaCrO4 was equivalent in the human and mouse cells, but was a factor of 4 less in the hamster cells. The single strand breaks were almost entirely repaired after an 18-h incubation in metal free medium in all three cell lines, whereas DNA-protein cross-links persisted in these cell lines in proportion to their initial levels. These results demonstrate differences in the sensitivity of human, hamster, and mouse cells to CaCrO4 and suggest that the repair-resistant DNA-protein cross-link may be important in mediating the long term toxic and carcinogenic effects of CaCrO4.