Microsomal Mixed-Function Oxidase and Activities of Some Related Enzymes in Hyperplastic Nodules Induced by Long-Term Griseofulvin Administration in Mouse Liver1

Hepatic hyperplastic nodules induced in mice by long-term griseofulvin administration were examined for selected microsomal activities and responses to enzyme inducers. Despite a decrease in microsomal cytochrome P-450 in hyperplastic nodules, aminopyrine N-demethylase was at control levels. Benzopyrene hydroxylase activity was slightly lower in microsomes derived from hyperplastic nodules than in those of control liver. Reduced nicotinamide adenine dinucleotide-cytochrome b5 reducÃ-ase was at control level, but reduced nico tinamide adenine dinucleotideand reduced nicotinamide ad enine dinucleotide phosphate (NADPH)-cytochrome c reductases and the NADPH-ferricyanide reductase were increased. NADPH-supported lipid peroxidation was lower in microsomes from hyperplastic nodules than in those from control liver, whereas microsomal stearoyl coenzyme A desaturase activity was almost doubled in the nodules. NADPH-cytochrome c redactases isolated and semipurified from hyperplastic nodule and from control liver microsomes showed almost identical affinity for NADPH. Microsomal enzymes of hyperplastic nod ules responded readily to phénobarbital induction, but sodium dodecyl sulfate-polyacrylamide gel electrophoresis disclosed differences in the polypeptide patterns in the molecular weight range from 47,000 to 54,000 between microsomes derived from hyperplastic nodules and control livers.