Exposure of cultured human proximal tubular cells to cadmium, mercury, zinc and bismuth: toxicity and metallothionein induction

The kidney, in particular the proximal convoluted tubule, is a major target site for the toxic effects of various metals. However, little is known abo ut the early effects of these metals after acute exposure in man. In the pr esent study we have evaluated the toxicity of several inorganic metal compo unds (CdCl2, HgCl2, ZnCl2, and Bi(NO3)(3)) and the induction of metallothio nein by these compounds in cultured human proximal tubular (HPT) cells for up to 4 days. The results showed that bismuth was not toxic even at the hig hest dose (100 mu M) used, while zinc, cadmium and mercury exhibited varyin g degrees of toxicity, zinc being the least toxic and mercury the most pote nt. A significant degree of interindividual variation between the different isolates used in these experiments was also observed. All metals used in t he present study induced MT, as revealed by immunocytochemistry. All metals showed maximal induction between 1 and 3 days after treatment. Although a certain amount of; constitutive MT was present in the cultures, the intensi ty of the staining varied with time in culture and between the different is olates studied. No correlation could be made between the intensity of the s taining in control cultures (indicating total amount of constitutive MT) an d the susceptibility of a given isolate to metal toxicity. Furthermore, no correlation could be : made between metal-induced MT and the susceptibility of a given isolate to that particular metal. (C) 1998 Elsevier Science Ire land Ltd. All rights reserved.