Distribution of Carbon Tetrachloride in Rat Liver and Its Urinary Metabolites

The incorporation of 14CCl4 into hepatic protein and its metabolites in the urine were investigated after the oral administration of 14CCl4 to rat and the following results were obtaind. 1) After the oral administration of 14CCl4, 2.7% and 3.6% of dosed 14C-radioactivity was excreted in the urine of 24 and 120 h, respectively. 2) 21.9% and 1.9% of the whole urinary radioactivity were in the form of urea and hippuric acid, respectively. In the radioactive hippuric acid, the benzoic acid moiety was labeled with 14C. 3) Among the liver cell fractions obtained 6 h after the oral administration, the ratio of specific radioactivities per weight of protein in nucleus, mitochondria, microsome and cytosol was about 1 : 1 : 3.5 : 2. As the result of dialysis of cytosol, 51.1% of the whole radioactivity was found to be bound to protein. 4) In the reaction mixture of in vitro metabolic experiment by using liver homogenate, radioactive benzoic acid was identified by the isotope dilution method and a peak corresponding to hippuric acid was observed on its TLC. 5) From the results mentioned above, it is assumed that radioactive benzoic acid, a precursor of hippuric acid found in the rat urine, might be originated from binding of 14C-labeled active metabolite of CCl4 to protein and secondly from liberating in phenyl-carboxyl form by the degradation of protein.