Cholesterol biosynthesis in transplantable hepatomas: evidence for impairment of uptake and storage of dietary cholesterol.
Cholesterol feeding inhibits cholesterol biosynthesis in normal but not in malignant liver tissue. It has been postulated that hepatomas have suffered a specific intracellular deletion of the cholesterol feedback control mechanism, but there is little direct evidence to support this hypothesis. Rats bearing Morris transplantable hepatomas were fed high cholesterol diets for periods of up to 21 days. Cholesterol biosynthesis, as expected, was suppressed in the normal liver but not in hepatomas. The livers accumulated large amounts of cholesteryl ester but the hepatomas showed little or no increase in ester content. Cholesterol-1alpha-(3)H was administered intragastrically to other tumor-bearing rats. Uptake of radioactivity by the tumors was much slower than by normal liver. Comparison of the specific activities of liver and tumor cholesterol with that of the plasma suggested that the liver took up dietary cholesterol selectively from the blood, while the appearance of radioactivity in the tumors could be explained by slow equilibration with plasma cholesterol. Our results suggest that the insensitivity of cholesterol biosynthesis to dietary cholesterol in hepatomas could be explained by an impairment in the uptake and storage of dietary cholesterol and that the concept of an intracellular deletion of the feedback mechanism requires further evidence.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism*; D002784:Cholesterol / Q000008:administration & dosage / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D004041:Dietary Fats / Q000378:metabolism*; D004952:Esters / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D005246:Feedback; D007408:Intestinal Absorption / Q000187:drug effects; D007441:Intubation, Gastrointestinal; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms; D009368:Neoplasm Transplantation; D051381:Rats; D014316:Tritium
D000085:Acetates; D002247:Carbon Isotopes; D004041:Dietary Fats; D004952:Esters; D014316:Tritium; D002784:Cholesterol