C-MYC IS NOT INVOLVED IN CADMIUM-ELICITED APOPTOTIC PATHWAY IN PORCINE KIDNEY LLC-PK1 CELLS

Cadmium chloride can induce DNA fragmentation, a biochemical character istics of apoptosis in renal epithelial LLC-PK1 cells. Studies of cadm ium cytotoxicity demonstrated that cadmium activates c-myc transcripti on. In this study, we investigated whether c-myc is a necessary compon ent of cadmium-induced apoptosis. By kinetic analysis, transient activ ation of c-myc transcript by cadmium occurred before DNA fragmentation was induced by the metal, indicating an apparent correlation between induction of c-myc mRNA and promotion of apoptosis. However, even when using actinomycin D to block transcriptional activation of c-myc, or antisense oligodeoxynucleotide complementary to c-myc to block transla tion of c-myc, cadmium could still induce apoptosis. Thus, our data sh ow that cadmium elicits apoptosis by a mechanism other than regulation of c-myc expression: transcriptional activation of c-myc during apopt osis is not always involved in the cell-death events.