A constitutive deficiency in the monooxygenase system of spontaneous mouse liver tumors.
Exposure to chemical carcinogens evokes a population of altered hepatocytes that demonstrates significantly diminished monooxygenase activity. It has been suggested that this alteration permits the target cell to escape the toxic effects of the carcinogen and proliferate. In an attempt to determine whether this enzyme defect has broader implications for the carcinogenic process, we examined the monooxygenase system and additional components of spontaneous hepatocellular tumors in mice with a genetic predisposition to tumorigenesis. These tumors uniformly demonstrated a significant deficit in cytochrome P-450 and aminopyrine N-demethylase, despite the absence of known carcinogens, toxins, or promoting agents in their environment. Tumors of similar histiotype induced by a small, single neonatal administration of diethylnitrosamine demonstrated identical alterations. This report, therefore, suggests a strong link between a genetic program for tumorigenesis and a deficit in the monooxygenase system in spontaneous tumors. Further, it reveals that a toxic-selective environment is not required for the expansion of the cell population that possesses this phenotype.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D016660:NAD(P)H Dehydrogenase (Quinone); D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011808:Quinone Reductases / Q000378:metabolism; D013045:Species Specificity; D000509:alpha-Fetoproteins / Q000032:analysis
D000509:alpha-Fetoproteins; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010089:Oxidoreductases, N-Demethylating; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D014453:Glucuronosyltransferase; D010634:Phenobarbital