The pattern of metabolism of 2-acetylaminofluorene in carcinogen-induced hepatocyte nodules in comparison to normal liver

Abstract

This study was designed to test further the hypothesis that the special biochemical pattern seen in hepatocyte nodules during liver carcinogenesis could be of fundamental importance in their selective metabolism of one carcinogenic xenobiotk, 2-AAF, as related to their resistance to xenobiotics. Nodules of a certain stage were induced using the resistant hepatocyte model. The metabolism of a single small dose of 2-AAF in hepatocyte nodules in comparison to normal liver was studied at different time intervals up to 30 h. The levels of free 2-AAF in nodules and in normal liver were approximately the same over the whole time period. However, the nodules showed a large decrease in the binding of 2-AAF to DNA, RNA and proteins as well as in the metabolic conversion to hydroxylated forms, both free and conjugated with glucuronic acid. The patterns of metabolic conversion to metabolites and of conjugation of the metabolites are in harmony with the known biochemical patterns in nodules, a decrease in phase I components involved in the metabolism of carcinogens and other xenobiotics and an increase in most phase II components involved in conjugation and detoxification.