Effects of the heavy metals cadmium and zinc on the regulation of cell destiny are reviewed in light of an apoptogenic metal of cadmium and the antiapoptotic nature of zinc. Exposure of renal cells to cadmium causes apoptotic features, DNA fragmentation and chromatin condensation in earlier stages of cadmium cytotoxicity than the cadmium-induced necrotic phase. The molecular mechanism of cadmium-induced apoptosis is poorly understood. Neither cadmium-metallothionein nor an immediate early gene such as c-myc is involved in the apoptotic pathway. In contrast, zinc can abolish cadmium-induced apoptosis. Although the mechanism underlying zinc inhibition of apoptosis remains uncertain, one possibility is that the ability of zinc to facilitate DNA synthesis might contribute to its protective effect on apoptosis.Key words ---apoptosis, cadmium, zinc *To whom correspondence should be addressed: Regional Environment Division, National Institute for Environmental Studies, Tsukuba 305-0053, Japan. Tel.: +81-298-50-2396; Fax: +81-298-50-2571; E-mail: ishidou@nies.go.jp Cadmium is a nephrotoxic metal.1) The proximal tubule of the mammalian kidney is a major target of chronic cadmium-induced toxicity.2) Cadmium chloride induces the synthesis of metallothionein in the liver, which, when released into circulation, is taken up by renal tubule cells.3) In the kidney, cadmium associated with metallothionein is degraded in lysosomal compartments, and the released cadmium in turn stimulates a cascade of toxic effects.
4)The development of cadmium-induced lesions in the kidney is characterized by proteinuria and excessive urinary excretion of other substrates such as enzymes, amino acids, and glucose.