Metabolic controls in precancerous liver: V. Loss of control of cholesterol synthesis during feeding of the hepatocarcinogen 3-methyl-4-dimethylaminoazobenzene

We have examined dietary control of cholesterol synthesis in rat liver during the feeding of 3′-methyl-4-dimethyl-aminoazobenzene (3′ MeDAB), using an assay which permits repeated tests on the same animal. Synthesis was measured as plasma levels of 7-dehydrocholesterol following a single dose of AY-9944 (trans1,4-bis (2-chlorobenzylaminomethyl) cyclohexane dihydrochloride), a drug which inhibits the conversion of 7-dehydrocholesterol to cholesterol. During 3′ MeDAB feeding there was a significant loss of inhibition of sterol synthesis in response to cholesterol feeding, but control rapidly returned to normal as soon as the carcinogen treatment was discontinued. The loss of control observed here was similar to that previously reported for 3 other hepatocarcinogens. © 1973.