Regulation and expression of four cytochromes P-450 isoenzymes, NADPH-cytochrome P-450 reductase, the glutathione transferases B and C and microsomal epoxide hydrolase in preneoplastic and neoplastic lesions in rat liver

A. Buchmann, Wolf D. Kuhlmann, M. Schwarz, W. Kunz,
C. R. Wolf, E. Moll, T. Friedberg, F Oesch


Institute of Biochemistry, German Cancer Research Centre, D-6900 Heidelberg, FRG
Imperial Cancer Research Fund, Medical Oncology Unit, Edinburgh, UK
Institute of Toxicology, University of Mainz, D-6500 Mainz, FRG

Nitrosamine-induced hepatocarcinogenesis has been used to investigate the regulation and expression of different drug-metabolizing enzymes in preneoplastic and neoplastic lesions in the female Wistar rat. Immunohistological studies were done with peroxidase (HRP) as marker. The enzymes investigated were two phenobarbital-inducible cytochrome P-450 (cyt. P-450) isoenzymes (PB1 and PB2, mol. wt. 52000 and 53500, respective-ly), two 3-methylcholanthrene-inducible forms (MC1 and MC2, mol. wt. 54500 and 57000, respectively), NADPH-cytochrome P-450 reductase, the cytosolic glutathione transferases (GSTs) B and C and the microsomal epoxide hydrolase with broad substrate specificity (mEHb).