An evaluation of tissue metallothionein and genetic resistance to cadmium toxicity in mice

Abstract

The role of metallothionein or metallothionein-like proteins (MT) in genetic resistance to the testicular and hepatic toxicity of cadmium was examined in inbred strains of mice. Mice of two strains resistant (AJ and C3H/HEJ) or susceptible (129J and DBA/2J) to cadmium-induced testicular necrosis were administered sc 30 mumol CdCl2/kg. The uptake of cadmium and the induction of MT in tissues were determined after 6 hr. The results showed that accumulation of cadmium in liver and kidney tissues of the four strains was very similar. MT levels were elevated up to 20-fold in the liver and up to almost 8-fold in the kidney, resulting in cadmium to MT molar ratios of 6.7 to 10.0 in the liver and 1.2 to 1.9 in the kidney. The greatest increase in hepatic MT as well as the cadmium to MT ratio was in the C3H/HEJ strain which is susceptible to cadmium-induced hepatotoxicity. Testicular cadmium levels were significantly elevated in the two susceptible strains. The basal levels of MT-like protein in the testis were generally higher than those in the kidney. Although, only the testis of 129J (susceptible) showed an increase in this protein after 6 hr, both susceptible strains injected with cadmium had significantly higher levels of the protein as compared to the resistant strains. The 30,000-Da cadmium-binding protein in AJ and CD-1 (susceptible) mouse strains was found to cross-react with the anti-MT-serum. Necrotic changes were visible in the testes of the susceptible strains as a result of cadmium administration. Immunohistochemically, there were no significant differences in the localization of MT in the liver, kidney or testis among the four strains. MT or an MT-like protein was concentrated mainly in the interstitial tissue of the mouse testis, but was also detected in the seminiferous tubules. It is concluded that the strain differences in acute toxicity of cadmium are probably not due to low MT concentration in tissues of the susceptible strains.