Accelerated regression of carcinogen-induced preneoplastic hepatocyte foci by peroxisome proliferators, BR931, 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio (N-B-hydroxyethyl)acetamide, and di-(2-ethylhexyl)phthalate.
Enzyme altered preneoplastic hepatocyte foci were induced in male Sprague Dawley rats by a single injection of diethylnitrosamine (DEN) followed by dietary promotion of a choline-deficient (CD) diet for 4 weeks or by feeding a diet containing 0.02% 2-acetylaminofluorene for 4 weeks. BR931, a hypolipidemic agent, administered to rats bearing preneoplastic foci caused a rapid regression of the foci within 4-6 weeks. Di(2-ethylhexyl)phthalate (DEHP), a plasticiser, exerted the similar effect when tested on rats bearing preneoplastic foci induced by DEN + CD diet. Since BR931 and DEHP have been shown to be carcinogenic after long term feeding, the results suggest that the short-term effects of the class of agents known as hypolipidemic peroxisome proliferators are different from the chronic effects. Alternatively, the precursor lesions of hepatocellular carcinomas induced by hypolipidemic, peroxisome proliferators may differ from enzyme altered hepatocytic foci.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002796:Choline Deficiency / Q000150:complications; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004052:Diethylnitrosamine; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D010795:Phthalic Acids / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000201:enzymology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000032:analysis
D000960:Hypolipidemic Agents; D010795:Phthalic Acids; D011743:Pyrimidines; D004052:Diethylnitrosamine; C016908:pirinixil; D004051:Diethylhexyl Phthalate; D005723:gamma-Glutamyltransferase