CADMIUM-INDUCED ELEVATION OF HEPATIC ISOMETALLOTHIONEIN CONCENTRATIONS IN INBRED STRAINS OF MICE

Susceptibility to Cd toxicity differs among inbred strains of mice. For example, C3H/He mice are sensitive to Cd-induced hepatotoxicity while DBA/2 mice are resistant. Metallothionein (MT), which in rodents exists predominantly as two isoproteins (MT-I and MT-II), is an important endogenous protein in the detoxication of Cd. The present investigation examines the possibility that strain-dependent susceptibility to Cd-induced liver injury is mediated by an inherited inability to accumulate a specific isoform of MT in response to Cd exposure. Hepatic concentrations of MT-I and MT-II were measured in C3H/He (Cd-sensitive) and DBA/2 (Cd-resistant) mice at various times after the administration of non-toxic (2.5-mu-mol Cd/kg) to hepatotoxic (80-mu-mol Cd/kg) dosages of Cd. The concentration of MT-I and MT-II in these strains was similar 24 h after injection of non-hepatotoxic dosages of Cd (10-mu-mol Cd/kg or less) as well as 6-12 h after a mildly hepatotoxic dose of Cd (20-mu-mol Cd/kg). The concentration of total MT in liver of Cd-sensitive mice was greater than that present in resistant mice 24-72 h after 20-mu-mol Cd/kg injection. The data indicates that susceptibility to Cd-induced hepatotoxicity observed in C3H/He mice is not due to a deficit in the induction of a particular isoform of MT.