APOPTOSIS IN RAT RENAL PROXIMAL TUBULAR CELLS INDUCED BY CADMIUM

Cadmium chloride can induce DNA fragmentation, a biochemical character istic of apoptosis in renal epithelial LLC-PK1 cells. This study was e xtended to determine the in vivo effects of this heavy metal on apopto sis. 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 th e kidney 12 h after injection of cadmium-metallothionein without a con current release of lactate dehydrogenase in urine. Cycloheximide (3 mg /kg) inhibited cadmium-induced DNA fragmentation, suggesting that prot ein synthesis might be required for the induction of cell death by thi s metal. Apoptotic cells were identified in proximal tubular cells by in situ DNA 3'-end labeling. Furthermore, chromatin condensation in th e apoptotic population of renal proximal tubular cells was noted. Data thus suggest that cadmium produces biochemical and morphological alte rations in kidney, which are characteristic features seen in apoptosis .