title: Immunochemical localization and functional characterization of cytochrome P450IIE1 in rat hepatocyte foci and nodules.
abstract: P450IIE1 was studied in rat hepatocyte foci and nodules from male Wistar rats, treated for 7 weeks with N-nitroso-morpholine (20, 40 and 80 mg/ml of drinking water). Livers were examined after 15, 23 and 31 weeks. Using specific anti-P450IIE1 IgG, different phenotypes of P450IIE1-altered foci were observed: (i) positive foci, predominant at early times and at the two lower dosages, (ii) negative foci and (iii) mixed-type foci consisting of P450IIE1-positive and -negative hepatocytes which were preponderant at 31 weeks. Immunoblotting of microsomes from livers containing foci and nodules obtained at week 31 of the experiment revealed a decrease in P450IIE1 level, which was correlated to decreased high affinity dimethylnitrosamine demethylase activity. The results suggest phenotypic heterogeneity of P450IIE1-altered foci with predominantly negative foci at later stages.
authors.affiliation: Institute of Toxicology, University of Tübingen, FRG.
authors.forename: A B
authors.initials: AB
authors.lastname: Kobusch
authors.forename: D
authors.initials: D
authors.lastname: Schrenk
authors.forename: G
authors.initials: G
authors.lastname: Gans
authors.forename: P
authors.initials: P
authors.lastname: Münzel
authors.forename: J
authors.initials: J
authors.lastname: Werringloer
authors.forename: M
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: K W
authors.initials: KW
authors.lastname: Bock
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D006965:Hyperplasia / Q000139:chemically induced / Q000201:enzymology; D007120:Immunochemistry; D008099:Liver / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009025:Morpholines; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009025:Morpholines; C031405:N-nitromorpholine; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating