The damage of the hepatic mixed functional oxygenase system by CCl4: significance of incorporation of 14CCl4 metabolites in vivo

The relation between incorporation of ¹⁴C from ¹⁴CCl₄ into liver lipids and damage to the mixed functional oxygenase system of liver microsomes was investigated in rats of different sex or differently pretreated. Under the respective conditions of pretreatment the ¹⁴C incorporation rate and the relative decrease of the cytochrome P-450 level as the parameters most influenced by CCl₄ were compared with those for untreated female rats. Induction by 3-methylcholanthrene does not after both parameters. Induction by sodium phenobarbital enhances the ¹⁴C incorporation rate as well as the cytochrome P-450 decrease but the latter is more affected. In male rats only the ¹⁴C incorporation rate increased. Vitamin D₃-pretreated rats showed a smaller decrease of cytochrome P-450 but an enhanced ¹⁴C incorporation rate. Therefore, there is no correlation between the cytochrome P-450 decrease and ¹⁴C incorporation rate. Reasons for the lack of that correlation are discussed with regard to the mechanism of liver cell damage by carbon tetrachloride.