Feedback control of cholesterol biosynthesis in rats fed the liver carcinogens benzidine and 2-acetylaminofluorene.

Dietary feedback control (DFC) of hepatic cholesterol synthesis is absent in hepatomas of trout, mouse, rat and man. DFC has also been shown to be defective in rats fed several liver carcinogens, including 2-acetylaminofluorene (AAF). These studies have led to the hypothesis that loss of normal DFC is an early and necessary event in the development of liver cancer. To test this hypothesis, we fed the liver carcinogens benzidine (0.006% in drinking water) or AAF (0.05% in chow) to male Sprague-Dawley rats for either 3 or 6 weeks. We measured cholesterol synthesis as the incorporation of 2-14C-acetate into digitonin-precipitable sterols by liver slices. DFC was tested by adding 2% cholesterol to the diet for 3 days prior to sacrifice. DFC was defective in the AAF-fed rats but was normal in the benzidine-treated rats. These results are at variance with the previously stated hypothesis and, for the first time, suggest that defective DFC is not a consistent finding in the early stages of liver carcinogenesis. Additional research is necessary to explain why DFC is altered by exposure to some liver carcinogens such as AAF but unaffected by exposure to others such as benzidine.