Deoxycholic-acid, But Not Lithocholic Acid, Modulates Rat-liver Carcinogenesis
(1992) The Cancer Journal (Print Edition) — Vol. 5, n° 2, p. 107-110 (1992)
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- The administration of high doses of secondary bile acids to animals is a toxic treatment, the main target organ of which is the liver. The aim of this study was to compare, in a long-term experiment, the modulating activity of deoxycholic acid (DCA) and of lithocholic acid (LCA) on rat liver carcinogenesis. DCA or LCA were given chronically at the dose of 0.5% in the diet in male Wistar rats previously submitted to the initiation- selection (IS) procedure (I = diethylnitrosamine 200 mg kg i.p.; S = acetylamino-fluorene 0.03% in the diet during 2 weeks, with 2 mg kg CCl4 in the middle of the treatment). Among the bile acids tested, only DCA positively modulates rat liver carcinogenesis by increasing the incidence and the yield of benign lesions after 17 weeks, and of malignant tumors after 35 weeks, as compared to IS alone. Moreover, the positive modulation induced by DCA is qualitatively different from that induced by phenobarbital (PB, 0.05% in the drinking water). Indeed, as in DCA- and PB-treated animals, the major types of cancers are of the glandular type (cholangiocellular carcinoma or hepatocellular carcinoma type IV), and of the hepatocellular carcinoma type I and II, respectively. The fact that DCA is a positive modulator of rat liver carcinogenesis, whereas LCA is not, could be explained by our previous results showing that when given orally to the rat, DCA accumulates in the liver, whereas LCA, which is metabolized to muricholic and other more hydrophilic (and therefore less toxic) metabolites, does not.
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Delzenne, N., Taper, H., & Roberfroid, M. (1992). Deoxycholic-acid, But Not Lithocholic Acid, Modulates Rat-liver Carcinogenesis. The Cancer Journal (Print Edition), 5(2), 107-110. https://hdl.handle.net/2078.5/63773 (Original work published 1992)