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To elucidate the possible toxicity of heavy metals in a renal tubular epithelial cell line derived from a normal cynomolgus female monkey (JTC-12, P3 (F], the effects of HgCl2, Na2CrO4 and NiCl2 on the dome formation and the release of intrinsic enzymes from the cells were studied. The results were as follows: 1. The JTC-12. P3(F) cells showed an evident dome formation when an inducer of differentiation (hexamethylene bisacetamide or N, N-dimethylformamide) was added to the medium. 2. Ouabain inhibited the dome formation of the JTC-12. P3(F) cells, suggesting that the dome formation is dependent on the active transepithelial transport of Na+. 3. The addition of 40 microM HgCl2, 10 microM Na2CrO4 or 20 microM NiCl2 inhibited the dome formation. 40 microM HgCl2, 10 microM Na2CrO4 or 150 microM NiCl2 caused significant cell death. 4. The addition of 5 microM HgCl2, 1 microM Na2CrO4 or 20 microM NiCl2 resulted in an increased release of lactate dehydrogenase into the medium for 6 hours. 20 microM HgCl2, 1 microM Na2CrO4 or 20 microM NiCl2 increased the medium gamma-glutamyl transpeptidase concentration for 6 hours, but 40 microM HgCl2, 5 microM Na2CrO4 or 100 microM NiCl2 did not cause a significant increase in the medium alkaline phosphatase concentration. The results suggest that the JTC-12. P3(F) cells possess, at least in part, functional characteristics similar to the other kidney proximal tubular cells and that the inhibition of dome formation and enzyme release from the cells may be the early indicators that predict metal toxicity to the cells.

Application of renal epithelial cell culture in study of organ toxicity of heavy metals.