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 shown that hexavalent chromium induces apoptosis in Chinese hamster ovary (CHO) cells, suggesting an association of apoptosis with carcinogenesis. In contrast, induction of apoptosis by cadmium has been inconsistently 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 evaluated by both agarose gel and in situ end-labeling methods. Apoptosis was observed at 48 h after treatment with 300 microM chromium (Na2CrO4) for 2 h. Cadmium alone at concentrations of 1, 5, or 10 microM (as CdCl2) did not induce apoptosis in these cells even at times up to 72 h after treatment. However, when CHO cells were concurrently exposed to cadmium 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 in metallothionein were not induced by these metal treatments. These findings indicate that cadmium can block chromium-induced apoptosis. The suppression of apoptosis by cadmium may be a significant aspect of its carcinogenic mechanism.
Shimada
H
H
Laboratory of Comparative Carcinogenesis and Office of Laboratory Animal Science, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland, USA.
Shiao
Y H
YH
Shibata
M
M
Waalkes
M P
MP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D002104:Cadmium / Q000494:pharmacology* / Q000633:toxicity; D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity; D002471:Cell Transformation, Neoplastic; D002857:Chromium / Q000494:pharmacology* / Q000633:toxicity; D006224:Cricetinae; D003412:Cricetulus; D004347:Drug Interactions; D066298:In Vitro Techniques; D008668:Metallothionein / Q000378:metabolism
D002273:Carcinogens; D002104:Cadmium; D002857:Chromium; D008668:Metallothionein