Decreased expression of cytochrome P-452 in the resistance phenotype characteristic of putative preneoplastic hepatocyte nodules during hepatocarcinogenesis.
Hepatocyte nodules, a characteristic early step in the development of liver cancer in rats, has a distinctive resistance phenotype including a large decrease in total cytochromes P-450 and in two isozymes induced by phenobarbital and two by 3-methylcholanthrene. In this study, it has been observed that the nodules show a large decrease in an additional cytochrome P-450, cytochrome P-452, which is very active in the hydroxylation of lauric acid at C-11 and C-12. The decrease in activity of this microsomal cytochrome P-452 is of the same order of magnitude as the decreases in the other cytochrome P-450 components. These observations are consistent with the hypothesis that there is some more basic alteration in the synthesis or availability of heme and that the changes in the activities of the cytochromes P-450 are secondary.
Roomi
M W
MW
Department of Pathology, University of Toronto, Ontario, Canada.
Bacher
M A
MA
Gibson
G G
GG
Parke
D V
DV
Farber
E
E
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000235:genetics / Q000378:metabolism*; D004351:Drug Resistance; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010641:Phenotype; D011230:Precancerous Conditions / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344
D003580:Cytochromes; C046362:cytochrome P-452; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D042926:Cytochrome P-450 CYP4A; D000633:Aminopyrine N-Demethylase