Ishido M, Tohyama C, Suzuki T
Environmental Health Sciences Division, National Institute for Environmental Studies, Onogawa, Tsukuba, Japan.
Life Sci. 1998;63(14):1195-204. doi: 10.1016/s0024-3205(98)00382-8.
Cadmium chloride can induce DNA fragmentation, a biochemical characteristics of apoptosis in renal epithelial LLC-PK1 cells. Studies of cadmium cytotoxicity demonstrated that cadmium activates c-myc transcription. In this study, we investigated whether c-myc is a necessary component of cadmium-induced apoptosis. By kinetic analysis, transient activation 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 translation of c-myc, cadmium could still induce apoptosis. Thus, our data show that cadmium elicits apoptosis by a mechanism other than regulation of c-myc expression: transcriptional activation of c-myc during apoptosis is not always involved in the cell-death events.