A relative deficiency of cytochrome P-450 and aryl hydrocarbon [benzo(a)pyrene] hydroxylase in hyperplastic nodules induced by 2-acetylaminofluorene in rat liver.
The concentrations of cytochrome P-450 and the activities of aryl hydrocarbon [benzo(a)pyrene] hydroxylase (AHH) and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase were measured in early (gray-white) and remodeled (brown) hyperplastic nodules induced in the livers of rats with 2-acetylaminofluorene and were compared to the values in control livers and in the liver surrounding the nodules. Cytochrome P-450 content of early (14 weeks) hyperplastic nodules is 30% of the activity of untreated control livers and 48% of the activity of the surrounding liver. AHH activity of the  early nodules is 10% of the control activity and 33% of the activity in the surrounding nonnodular liver. Nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity in the microsomes of early nodules is 76% of the control activity and 78% of the activity in the surrounding liver. In the late remodeled nodules, (22 and 25 weeks), the cytochrome P-450 content is 40% of that of controls and AHH activity is 15% of the control activity. In primary hepatomas induced by 2-acetylaminofluorene, cytochrome P-450 content is 21% of that of controls, AHH activity is 11% of the activity of controls, and reductase is 50% of the control activity. These results, indicating a relative nodule deficiency in some of the cellular components believed to be important in the activation of hepatocarcinogens and hepatotoxins, offer one possible explanation for the relative resistance to carcinogen cytotoxicity of hyperplastic liver nodules.
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003864:Depression, Chemical; D005449:Fluorenes / Q000494:pharmacology*; D006965:Hyperplasia / Q000201:enzymology; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D005449:Fluorenes; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D009251:NADPH-Ferrihemoprotein Reductase