Role of Metallothionein in Induced Resistance to Cadmium Toxicity in Isolated Rat Hepatocytes

Abstract

In order to investigate the fundamental role of metallothionein in the cellular response to cadmium exposure, a model system based on the primary suspension culture of isolated rat hepatocytes was developed. Inhibition of intracellular protein synthesis was utilized as an index of the effect of cadmium on intracellular metabolism. Comparative studies between hepatocytes prepared from control rats (naive hepatocytes) and from rats injected with 20 mg Zn²⁺/kg (s.c.) 24 hr prior to experimentation (Zn-preinduced hepatocytes) indicate that the presence of intracellular Zn-MT significantly reduces cadmium toxicity in the model system. Furthermore, this effect can be fully explained by the ability of the preinduced Zn-MT to sequester intracellular cadmium taken up during the subsequent exposure. These data strongly support the hypothesis that the resistance to cadmium toxicity conferred by pre-exposure to zinc is solely due to the cadmium binding capacity of preinduced Zn-MT.