CADMIUM SUPPRESSES APOPTOSIS INDUCED BY CHROMIUM

Cadmium and chromium are both well-known human carcinogens, and common exposures to these metals are not infrequent. Recent studies have sho wn that hexavalent chromium induces apoptosis in Chinese hamster ovary (CHO) cells, suggesting an association of apoptosis with carcinogenes is. In contrast, induction of apoptosis by cadmium has been inconsiste ntly observed. The present study was designed to determine if cadmium could induce apoptosis in CHO cells and if common exposure to cadmium and chromium would modify any apoptotic response. Apoptosis was evalua ted by both agarose gel and in situ end-labeling methods. Apoptosis wa s observed at 48 h after treatment with 300 mu M chromium (Na2CrO4) fo r 2 h. Cadmium alone at concentrations of 1, 5, or 10 mu M (as CdCl2) did not induce apoptosis in these cells even at times up to ;2 h after treatment. However, when CHO cells were concurrently exposed to cadmi um and chromium, chromium-induced apoptosis was markedly suppressed in a cadmium concentration-related fashion. Cadmium did not consistently modify the cytotoxic effects of chromium, and significant increases i n metallothionein were not induced by these metal treatments. These fi ndings indicate that cadmium can block chromium-induced apoptosis. The suppression of apoptosis by cadmium may be a significant aspect of it s carcinogenic mechanism.