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.