Effects of bromobenzene and carbon tetrachloride on the synthesis and release of proteins by perfused rat liver

Abstract

The effects of bromobenzene and carbon tetrachloride (CCl 4) on the hepatic incorporation of 14C- l-leucine into protein were compared to ascertain the relationship between liver necrosis and impairment of radiolabeled protein synthesis and release caused by these toxicants. Male rats were treated with bromobenzene or CCl 4 and 4 or 12 hr later the livers were removed and perfused in vitro in a recirculating perfusion apparatus. At 4 hr after its administration, CCl 4 only slightly impaired the rate of synthesis of radiolabeled proteins (liver + serum) but markedly decreased the release of radiolabeled proteins into the serum (perfusate). At 4 hr after the administration of bromobenzene, the rates of incorporation of 14C- l-leucine into proteins and the release of radiolabeled proteins were not appreciably changed. At 12 hr after bromobenzene pretreatment, the rate of radiolabeled protein synthesis was not altered when compared to that of control livers, but the release of 14C-labeled proteins into the perfusate was decreased. After pretreatment of rats with phenobarbital, bromobenzene decreased the synthesis and the release of 14C-labeled proteins (4 hr). β-Diethylaminoethyl diphenylpropylacetate (SKF 525-A) and 3-methylcholanthrene (3-MC) did not alter the effect of bromobenzene on the accumulation of total radiolabeled protein synthesis, while SKF 525-A, but not 3-MC, blocked the ability of bromobenzene to decrease the release of 14C-labeled proteins into serum. Since bromobenzene does not alter the rate of 14C-labeled protein synthesis at either 4 or 12 hr after administration, impairment of protein synthesis is probably not a primary cause of bromobenzene-induced liver necrosis. Evidence is presented suggesting that the decrease in the release of 14C- labeled proteins in the perfusate is due to changes in the pattern of protein synthesis as well as to decreases in the rate of protein synthesis.