Characterization of drug-metabolizing systems in hyperplastic nodules from the livers of rats receiving 2-acetylaminofluorene in their diet

Abstract

A number of drug-metabolizing systems were measured in hyperplastic noduli from the livers of rats receiving 2-acetyl-aminofluorene in their diet and compared with corresponding activities in control liver. The level of microsomal cytochrome P-450 is reduced 54% in the nodular tissue, while 5 activities catalyzed by the cytochrome P-450 system (i.e., aminopyrine N-demethylase, benzo[a]pyrene monooxygenase, ethoxyresorufin O-deethylase, ethoxycoumarin O-deethylase, and 2-acetylaminofluorene N-hydroxylase) are all present at levels corresponding to 5-44% of the control levels. The pattern of 2-acetylaminofluorene metabolites formed by nodule microsomes also differs from the pattern observed with control microsomes. Microsomal epoxide hydrolase is increased 415%, cytosolic glutathione S-transferases 203-576%, microsomal UDP-glucuronyltransferase activity about 200%, and cytosolic DT-diaphorase 1210% in the nodules. The same changes are seen in nodules of different sizes and in individual nodules of the same size. Finally, of all of these changes only the full increase in epoxide hydrolase can be seen after 1-3 weeks of exposure to 2-acetylaminofluorene.