Metabolic controls in precancerous liver—VII. Time course of loss of dietary feedback control of cholesterol synthesis during carcinogen treatment

Abstract

A technique is described, involving continuous low-level feeding of AY 9944 (trans- 1,4-bis(2-chlorobenzyl-aminomethyl) cyclohexane dihydrochloride), whereby the dietary feedback status of hepatic cholesterol synthesis in individual rats can be monitored at frequent intervals. Use of this technique has shown that the hepatocarcinogens ethionine ( 0·25% in feed) and methylazoxymethanol acetate (MAM-acetate) ( 50 mg/kg of body wt. i.p.) cause a rapid and sudden loss of feedback inhibition of hepatic cholesterol synthesis at approximately 7–9 and 11–14 days respectively. Loss of control is not caused by the non-carcinogenic hepatotoxin carbon tetrachloride.