Effect of dithiocarb and dimethyl sulfoxide on irreversible binding of 14C-bromobenzene to rat liver microsomal protein.

The irreversible binding of [14C]-bromobenzene to rat liver microsomal protein in vitro was inhibited by dithiocarb and DMSO. Dithiocarb suppressed this binding in a time- and concentration-dependent manner (I50 = 4.5 10(-5) M). DMSO reduced the degree of covalent binding by 61% from 5 x 10(-5) M to 8 x 10(-4) M. Dithiocarb was also effective in inhibiting irreversible binding of bromobenzene to liver protein in vivo. Our results are consistent with the hypothesis that dithiocarb exerts its antihepatotoxic efficacy by depressing microsomal mixed-function oxidase activity.