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Metabolism of Bile Components during Hepatocarcinogenesis

I. Conjugation of Cholic Acid in Vitro in Experimental Liver Carcinogenesis^*

Curtis L. Songster, Sydney S. Schochet, Jr. and Emmanuel Farber

( Departments of Pathology and Biochemistry, Tulane University School of Medicine, New Orleans, Louisiana)

The conjugation of cholic acid with taurine was measured in liver microsomes and supernatant from male rats (a) fed diets containing ethionine, 3'-methyl-dimethylaminoazobenzene (3'-Me-DAB), or 2-acetylaminofluorene (2-AAF) or (b) subjected to ligation of the common bile duct. A fairly rapid decrease in in vitro conjugation was found in the livers of the animals fed ethionine, beginning 2 days after initiation of the diet and reaching a minimum value of less than 1 per cent of the control level within 10–14 days. The defect in conjugation persisted for as long as the ethionine was fed (34 days). The level of conjugation returned to the control value within 10 days after the ethionine was removed from the diet. A similar defect was not found in the livers of rats fed 3'-Me-DAB or 2-AAF under conditions which lead to the development of liver cancer. Rats subjected to bile duct ligation also showed no defect in taurocholate synthesis.

Since ethionine, 3'-Me-DAB, 2-AAF, and bile duct ligation all induce a similar proliferation of bile duct epithelial cells, it must be concluded that the defect in conjugation of cholic acid with taurine cannot be of significant importance as a biochemical basis for the ductular proliferation. If there is truly a relationship between alterations in the metabolism of bile components or in bile secretion and the development of ductular proliferation, the metabolic correlate must be found in reactions other than the conjugation of cholic acid with taurine.

^* This research was supported in part by grants from the National Institutes of Health, the United States Public Health Service, the American Cancer Society, and the Life Insurance Medical Research Fund.

Recipients of Research Fellowships from a Medical Student Research Grant from the United States Public Health Service (CLS-1957-1958 and SSS-1959-1960).

American Cancer Society Research Professor of Pathology and Biochemistry. Present address: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh 13, Pennsylvania.

Received 3/ 8/63.