Immunochemical localization and functional characterization of cytochrome P450IIE1 in rat hepatocyte foci and nodules.
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.
Kobusch
A B
AB
Institute of Toxicology, University of Tübingen, FRG.
Schrenk
D
D
Gans
G
G
Münzel
P
P
Werringloer
J
J
Ingelman-Sundberg
M
M
Bock
K W
KW
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
D009025:Morpholines; C031405:N-nitromorpholine; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating