Cadmium-induced metallothionein synthesis in the rat liver slice system.

In vivo exposure of a rat to cadmium results in elevation of the hepatic metal-binding protein, metallothionein (MT). The present work describes the induction of MT in the in vitro liver slice system. Incubation of rat liver slices with CdCl(2) resulted in a dose-dependent elevation of tissue MT. The cadmium-binding protein was increased by 140 and 220% in the presence of 10 and 20 mum CdCl(2), respectively. A lower level (5 mum) of the inducer had only a slight effect. A time-course study showed a gradual increase in the MT level following incubation of the liver slices for 4 and 6 hr with 10 mum-cadmium. Characterization of the metal-binding protein by Sephadex G-75 gel filtration revealed that it is composed of MT and also of a high-molecular-weight fraction that might be either a polymerized or aggregated form of MT, or another type of cadmium-binding protein. These findings indicate that the response of the liver slice system to toxic agents is similar to that of the intact animal. These are encouraging results which need to be extended before the system can be introduced into the routine screening of hepatotoxic agents.