CADMIUM INDUCES APOPTOSIS IN A HUMAN T-CELL LINE

Cadmium, a potent toxic metal, poses a serious environmental threat bu t the mechanisms of its toxicity remain unclear. In the present study, we investigated the nature of cadmium-induced cell death in the human T cell line CEM-C12. Cadmium was time- and dose-dependently toxic for CEM-C12 cells, cell death being preceded by chromatin condensation an d DNA fragmentation. Quantification of the latter indicated an increas e above 4 mu M cadmium, with maximal fragmentation at 8 to 10 mu M. By contrast, when CEM-C12 cells were exposed to higher cadmium concentra tions (50 mu M), cell death increased without concomitant chromatin co ndensation or DNA fragmentation. Thus, cadmium at low and high concent ration kills CEM-C12 cells by apoptosis and necrosis, respectively. Ad dition of cycloheximide reduced the apoptotic effect of cadmium, sugge sting that cadmium-induced apoptosis is an process depending on protei n synthesis. Verapamil, a calcium-potassium channel blocker, markedly increased the viability of CEM-C12 cells treated by low cadmium concen trations and prevented DNA fragmentation. The apoptotic effect of cadm ium suggests a possible mechanism for lymphocyte damage occurring afte r in vivo exposure to cadmium.