Rodilla V, Miles A T, Jenner W, Hawksworth G M
Department of Medicine, University of Aberdeen, UK.
Chem Biol Interact. 1998 Aug 14;115(1):71-83. doi: 10.1016/s0009-2797(98)00059-3.
The kidney, in particular the proximal convoluted tubule, is a major target site for the toxic effects of various metals. However, little is known about the early effects of these metals after acute exposure in man. In the present study we have evaluated the toxicity of several inorganic metal compounds (CdCl2, HgCl2, ZnCl2, and Bi(NO3)3) and the induction of metallothionein 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 highest dose (100 microM) used, while zinc, cadmium and mercury exhibited varying degrees of toxicity, zinc being the least toxic and mercury the most potent. A significant degree of interindividual variation between the different isolates used in these experiments was also observed. All metals used in the 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 intensity of the staining varied with time in culture and between the different isolates studied. No correlation could be made between the intensity of the staining in control cultures (indicating total amount of constitutive MT) and 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.
肾脏，尤其是近端曲管，是各种金属毒性作用的主要靶位点。然而，对于人体急性接触这些金属后的早期影响却知之甚少。在本研究中，我们评估了几种无机金属化合物（氯化镉、氯化汞、氯化锌和硝酸铋）的毒性，以及这些化合物在培养的人近端肾小管（HPT）细胞中长达4天对金属硫蛋白的诱导作用。结果表明，即使在所用的最高剂量（100微摩尔）下，铋也没有毒性，而锌、镉和汞表现出不同程度的毒性，锌的毒性最小，汞的毒性最强。在这些实验中使用的不同分离株之间还观察到了显著的个体间差异。如免疫细胞化学所示，本研究中使用的所有金属都诱导了金属硫蛋白的产生。所有金属在处理后1至3天表现出最大诱导作用。尽管培养物中存在一定量的组成型金属硫蛋白，但染色强度随培养时间以及所研究的不同分离株而变化。对照培养物中的染色强度（表明组成型金属硫蛋白的总量）与给定分离株对金属毒性的敏感性之间没有相关性。此外，金属诱导的金属硫蛋白与给定分离株对该特定金属的敏感性之间也没有相关性。
