The ultrastructure and adaptation of altered hepatocytes, from the presumed premalignant nodules, induced by feeding acetylaminofluorene to rats, will be studied in monolayer culture after dissociating the liver cells by collagenase perfusion. The new cell populations will be identified by the presence of gamma-glutamyl transpeptidase and they will be further subdivided into less and more autonomous variants on the basis of their autoradiographic nuclear labelling index after in-vivo injection of H-TdR. Their length of survival and resistance to AAF will also be determined. Selected aspects of cholesterol and bile acid synthesis in the induced lesions will also be studied in-vitro and in-vivo by assaying the levels of these pathways' respective rate controlling enzymes, HMG-CoA reductase and cholesterol 7 alpha hydroxylase and by determining the level of cholesterogenesis, reflected by in-vivo incorporation of 3H2O into cholesterol-H. The perturbing of bile acid and cholesterol synthesis through dietary, hormonal and drug treatments should alter the activities of the enzymes in distinctive ways in norman liver. These alterations may then also be studied in preneoplastic and neoplastic liver to learn whether a change from normal is due to tumor progression or if it represents a more basic effect of hepatic carcinogenesis.
NIH ExPorter
NIH ExPorter