Sensitive response of cultured vascular smooth-muscle cells to cadmium cytotoxicity: comparison with cultured vascular endothelial cells and kidney epithelial LLC-PK1 cells.

Response to cadmium cytotoxicity of cultured bovine aortic smooth-muscle cells was compared with that of cultured bovine aortic endothelial cells and porcine kidney epithelial LLC-PK1 cells. The cell damage was evaluated by morphology and the lactate dehydrogenase leakage assay. It was found that vascular smooth-muscle cells are markedly sensitive to cadmium cytotoxicity. The accumulation of intracellular cadmium was much higher but that of metallothionein was much less in vascular smooth-muscle cells than in LLC-PK1 cells; vascular endothelial cells were in between vascular smooth-muscle cells and LLC-PK1 cells. The content of reduced glutathione was slightly increased by cadmium in all three cell types. The present data suggest that a much lower inducibility of metallothionein with a high accumulation of intracellular cadmium in vascular smooth-muscle cells resulted in a marked sensitivity of the cells to cadmium cytotoxicity. Vascular smooth-muscle cells may be one of the critical target of cadmium toxicity.

Induction of metallothionein synthesis by bismuth in cultured vascular endothelial cells.

Metallothionein synthesis induced by bismuth nitrate was characterized using a cell culture system. It was found that bismuth (1-10 microM) significantly increased the intracellular accumulation of metallothionein in bovine aortic endothelial cells without an exhibition of cytotoxicity and a change of either general protein synthesis or proliferative DNA synthesis after a 24-h incubation. A low increase in the metallothionein accumulation was observed in bovine aortic smooth muscle cells; however, porcine kidney epithelial LLC-PK1 cells, human Chang liver cells and two human hepatoma cell lines (HLF cells and Hep-G2 cells) did not respond to bismuth. Other cations including cobalt, lead and zinc at 10 microM failed to induce metallothionein in endothelial cells, although cadmium at 1 microM was a strong inducer. Bismuth accumulated highly in endothelial cells but very slightly in LLC-PK1 cells and Chang liver cells. The present data suggest that bismuth is a selective inducer of metallothionein of vascular endothelial cells and this cell type particularly responds to the cation.