Cadmium hypersusceptibility in the C3H mouse liver: cell specificity and possible role of metallothionein.

The possible involvement of metallothionein (MT) gene expression dysfunction was examined in a strain of mouse which is unusually sensitive to cadmium toxicity, the C3H. C3H mice, and the relatively cadmium-insensitive Swiss mice, were injected sc with 20 microM CdCl2/kg body wt. This dose caused liver damage, visible at the light microscopic level, in the C3H but not the Swiss mice. These studies showed that MT-I mRNA and MT protein accumulation, as well as binding of cadmium by MT, were very similar in the two strains. These data suggested that altered expression of MT in the hepatic parenchyma was not a factor in the C3H hypersusceptibility. An electron microscopic examination of the early effects of cadmium injection indicated that the primary targets for toxicity in the C3H liver may be the endothelial cells. It is hypothesized that the widespread damage seen at later times resulted, secondarily, from ischemia produced in response to endothelial cell damage.