Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis.
Hepatocyte ("hyperplastic") nodules induced in the liver by initiation with diethylnitrosamine and selected by dietary 2-acetylaminofluorene plus partial hepatectomy ("resistant hepatocyte model") have a special pattern of biochemical behavior and metabolic activity different than that seen acutely with many xenobiotics including many promoting agents and carcinogens. The nodule cells show a very low uptake of 2-acetylaminofluorene, relative to surrounding and normal liver, low levels of activity in the cytochromes P-450 and aryl hydrocarbon hydroxylase, high levels of activity in gamma-glutamyltransferase, microsomal epoxide hydrolase, soluble glutathione-S-transferase and soluble UDP-glucuronyltransferase (UDP-GT(1)) and elevated levels of glutathione. This metabolic pattern appears to maximize the resistance of the nodules to xenobiotics generally, such as 2-acetylaminofluorene, and thereby may account for the resistant behavior of nodule hepatocytes to the inhibition of cell proliferation and the cytotoxicity by 2-acetylaminofluorene and other carcinogens. The possible importance of this seemingly new metabolic program in carcinogenesis is discussed briefly.
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004052:Diethylnitrosamine / Q000494:pharmacology; D004351:Drug Resistance; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
D002273:Carcinogens; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene