Cadmium-induced apoptosis in murine fibroblasts is suppressed by Bcl-2

We investigated the induction of apoptosis by cadmium in NIH 3T3 murine fib roblasts. Apoptosis was triggered effectively by 10 muM CdCl2 within 24 h u nder which conditions cell viability was reduced by 50%. Cadmium-induced ap optosis was demonstrated by both morphological and biochemical analysis. We have shown that cadmium concentrations of 5-20 muM caused nuclear fragment ation. Moreover, internucleosomal DNA fragmentation was evoked by 10-25 muM CdCl2 within 24 h, as detected by the formation of ladder patterns in DNA electrophoresis. Since the induction of programmed cell death occurs togeth er with modifications in the cell cycle, we examined the ability of cadmium to block cell divisions by using a 5-bromo-2-deoxy-uridine incorporation a ssay. Our results indicate that about 40% of treated cells are blocked in G (0)-G(1) phase when exposed to 10 muM cadmium for 27 h. Finally, we address ed the question of whether the effect of cadmium could be prevented by supp ressing apoptosis. Over-expression of the anti-apoptotic protein Bcl-2 in N IH 3T3 cells protects against cadmium toxicity, thus suggesting a role for Bcl-2 in the regulation of cadmium-induced apoptosis.