Changes in activities of uridine diphosphate-glucuronyltransferases during chemical hepatocarcinogenesis

Changes in the activities of hepatic uridine diphosphate-glucuronyltransferases (UDP-GTs) were investigated during the induction of hyperplastic nodules (enzyme-altered foci) by a system consisting of diethylnitrosamine (DEN) followed by N-2-fluoroenylacetamide (FAA) and including partial hepatectomy. The activity of the late fetal form of UDP-GT, which was assayed towards o-aminophenol (o-GT activity), was induced rapidly by a single ip injection of DEN (200 mg/kg) or 3-methylcholanthrene (40 mg/kg) or by the continuous administration of FAA (0.02% in diet) alone. This activity further increased with the appearance of the nodules, while the activity of the neonatal form, which was assayed toward phenolphthalein (p-GT activity) and was inducible by phenobarbital, increased only slightly. The increased o-GT activity showed a good correlation with the increased number or area of enzyme-altered foci detected by gamma-glutamyltransferase activity staining, but the p-GT activity did not, though it was significantly increased. In hyperplastic nodules and well differentiated hepatomas induced by DEN (0.1% in drinking water, 3 weeks) but isolated long after cessation of DEN, o-GT activity was markedly increased, but p-GT activity was decreased or remained at the level of normal rat liver. These data indicate that the increased o-GT activity may be one of the enzyme markers for preneoplastic hepatic cells. An antioxidant, butylated hydroxyanisole (BHA) (0.75% in diet), markedly elevated the hepatic o-GT activity rapidly after being administered with FAA in the above system, and the induction of the nodules was inhibited.