Cadmium induces apoptosis in a human T cell line.
Cadmium, a potent toxic metal, poses a serious environmental threat but 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 and DNA fragmentation. Quantification of the latter indicated an increase above 4 microM cadmium, with maximal fragmentation at 8 to 10 microM. By contrast, when CEM-C12 cells were exposed to higher cadmium concentrations (50 microM), cell death increased without concomitant chromatin condensation or DNA fragmentation. Thus, cadmium at low and high concentration kills CEM-C12 cells by apoptosis and necrosis, respectively. Addition of cycloheximide reduced the apoptotic effect of cadmium, suggesting that cadmium-induced apoptosis is an process depending on protein synthesis. Verapamil, a calcium/potassium channel blocker, markedly increased the viability of CEM-C12 cells treated by low cadmium concentrations and prevented DNA fragmentation. The apoptotic effect of cadmium suggests a possible mechanism for lymphocyte damage occurring after in vivo exposure to cadmium.
el Azzouzi
B
B
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 200, Clamart, France.
Tsangaris
G T
GT
Pellegrini
O
O
Manuel
Y
Y
Benveniste
J
J
Thomas
Y
Y
D017209:Apoptosis / Q000502:physiology*; D002104:Cadmium / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002104:Cadmium; D004247:DNA; D014700:Verapamil