Hepatic metabolism and carcinogenesis. Its role in hepatoma and adenocarcinoma.
The effect of carcinogenesis on various hepatic microsomal parameters and related cell functions was studied in two tumor models. Hepatocarcinoma was produced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) (Solt-Farber model) and mammary adenocarcinoma using R3230 AC cancer cell line. In these models the effect of the tumor on metabolic functions of hepatocytes was studied. In the DEN/2AAF tumor model in nodules phase I components (cytochrome P-450, aminopyrine N-demethylase, arylhydrocarbon hydroxylase) were reduced, together with microsomal progesterone content and total and specific progesterone binding. Phase II components (glutathione, glutathione S-acyltransferase, UDP-glucuronyl transferase, epoxide hydrolase) were increased. In hepatoma the effects were more enhanced. Nodules grown in the speen retained the dedifferentiated enzyme characteristics. In the R3230 AC mammary adenocarcinoma phase I components of the hepatic endoplasmic reticulum were reduced, and phase II components increased. Progesterone content and receptor binding were also increased. These results indicate that enzymatic abnormalities in the liver cell are connected with cancer production and the hepatic dedifferentiation seems to be indistinguishable in tumor-bearing liver from those seen with extrahepatic neoplasms.
Feuer
G
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Department of Clinical Biochemistry, University of Toronto, Canada.
D000230:Adenocarcinoma / Q000139:chemically induced*; D000633:Aminopyrine N-Demethylase / Q000032:analysis; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000032:analysis; D008862:Microsomes, Liver / Q000032:analysis; D011374:Progesterone / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
D011374:Progesterone; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase