INDUCTION OF METALLOTHIONEIN MESSENGER-RNA AND PROTEIN FOLLOWING EXPOSURE OF CULTURED HUMAN PROXIMAL TUBULE CELLS TO CADMIUM

Humans have a complex expression of metallothionein (MT) genes which involves many MT isoforms encoded by a family of genes containing an upper limit of 12 possible functional genes, in contrast to most animals which have one or two functional MT genes. In the present study, human proximal tubule (HPT) cells were exposed to cadmium (Cd) to determine if these cultures might serve as a model system to study MT gene expression in the renal proximal tubule. Three independent isolates of HPT cells were shown to repeatably induce MT protein when exposed continually to a non-toxic dose of 1 mug/ml of Cd administered as CdCl2. Accumulation of MT protein was noted within 3 h and persisted over the 16-day time course. The expression of mRNA for the MT-IIA, MT-IA, B, E, F and G genes was also assessed through 16 days of exposure to 1 mug/ml of Cd versus control media. Of these, the mRNA for the MT-IIA, MT-IE, MT-IF and MT-IG genes were detected in the cells exposed to 1 mug/ml of Cd. Overall, the results were supportive that the HPT cells can provide a valuable model system to study the regulation of MT gene expression as it applies to the human renal proximal tubule.