Apoptosis in rat renal proximal tubular cells induced by cadmium.

Cadmium chloride can induce DNA fragmentation, a biochemical characteristic of apoptosis in renal epithelial LLC-PK, cells. This study was extended to determine the in vivo effects of this heavy metal on apoptosis. Nephrotoxicity was induced by a single intravenous administration of cadmium-metallothionein (0.15 mg metallothionein-bound cadmium/kg body weight) to male Jcl:Wistar rats. DNA fragmentation was seen in the kidney 12 h after injection of cadmium-metallothionein without a concurrent release of lactate dehydrogenase in urine. Cycloheximide (3 mg/kg) inhibited cadmium-induced DNA fragmentation, suggesting that protein synthesis might be required for the induction of cell death by this metal. Apoptotic cells were identified in proximal tubular cells by in situ DNA 3'-end labeling. Furthermore, chromatin condensation in the apoptotic population of renal proximal tubular cells was noted. Data thus suggest that cadmium produces biochemical and morphological alterations in kidney, which are characteristic features seen in apoptosis.