Application of Renal Epithelial Cell Culture in Study of Organ Toxicity of Heavy Metals

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 40μM HgCl2, 10μM Na2CrO4 or 20μM NiCl2 inhibited the dome formation. 40μM HgCl2, 10μM Na2CrO4 or 150μM NiCl2 caused significant cell death. 4. The addition of 5μM HgCl2, 1μM Na2CrO4 or 20μM NiCl2 resulted in an increased release of lactate dehydrogenase into the medium for 6 hours. 20μM HgCl2, 1μM Na2CrO4 or 20μM NiCl2 increased the medium γ-glutamyl transpeptidase concentration for 6 hours, but 40μM HgCl2, 5μM Na2CrO4 or 100μM 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.