CHANGES IN BILE-ACIDS METABOLISM DURING RAT HEPATOCARCINOGENESIS - CAUSATIVE OR UNRELATED

In the present paper, we have aimed at studying the variations in the metabolism of bile acids occuring during an hepatocarcinogenic process induced in male Wistar Rats by the biphasic protocol of Solt and Farb er(1). Bile acids concentrations was measured in the liver. The most s ignificant changes have been observed 5 weeks after the benining of th e treatment, it means one week after the selection treatment consistin g in 2-acetylaminofluorene administration : the increase in cholic aci d, and of its intestinal metabolite, deoxycholic acid, and of alpha- a nd beta- muricholic acids, are likely to be a consequence of an acute effect of 2acetylaminofluorene. To test for the putative implication o f liver bile acids modifications in the selection effect of 2-acetylam inofluorene, diethyl-nitrosamine-pretreated rats were fed a diet conta ining 1% lithocholic acid, a treatment that induces essentially the sa me qualitative changes in liver bile acids, as 2-acetylaminofluorene d oes : no selection effect of lithocholic acid could be demonstrated. T hese results suggest that changes in bile acid metabolism occuring ear ly in hepatocarcinogenesis are more likely to be secondary than causat ive events. The same conclusion comes from the results obtained later on in the process, where there is only a high increase in liver cholic acid and deoxycholic acid concentrations.