Synthesis and degradation of hepatic metallothionein in mice differing in susceptibility to cadmium mortality

Abstract

We have confirmed the observations of Tsunoo et al. (Toxicol. Lett. 4:253, 1979) that (a) DBA/2 mice are resistant to cadmium mortality than C3H mice and (b) DBA/2 mice accumulate more 109Cd into hepatic metallothionein than do C3H mice in response to an injection of 30 mumol CdCl2/kg, a dose of CdCl2 which is lethal to C3H mice. We now report, using a nonlethal dose of 8 mumol CdCl2/kg, that the rates of both the synthesis and the degradation of cadmium-induced hepatic metallothionein are increased in C3H mice. The rate of metallothionein synthesis, measured 6 hr after cadmium administration and expressed as the percentage of injected [35S]cysteine incorporated into metallothionein/g liver, was 0.33 +/- 0.04% (SD) in C3H mice, compared to 0.19 +/- 0.06% in DBA/2 mice (significantly different rates by Students' t test. P less than 0.01). Also, at this dose, hepatic 35S-labeled metallothionein was degraded with a half-life of 22.5 +/- 0.7 hr in C3H mice, compared to 30.1 +/- 2.5 hr in DBA/2 mice (significantly different half-lives by F test, within 95% confidence limits). The increased accumulation of metallothionein in resistant DBA/2 mice compared to sensitive C3H mice after cadmium exposure appears to be due primarily to a difference in metallothionein degradation, rather than metallothionein synthesis.