title: Effects of modifying agents on conformity of enzyme phenotype and proliferative potential in focal preneoplastic and neoplastic liver cell lesions in rats.
abstract: Development of preneoplastic lesions in the rat liver under the influence of various modifiers was investigated with particular attention to changes in simultaneous expression of altered enzyme phenotype within the lesions (conformity) and proliferation potential. Degree of conformity of marker enzymes such as glutathione S-transferase placental form (GST-P), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, adenosine triphosphatase and gamma-glutamyltranspeptidase was compared with levels of 5-bromo-2-deoxyuridine labeling. After initiation with diethylnitrosamine, rats were administered the hepatopromoter sodium phenobarbital (PB, 0.05%), the antioxidant ethoxyquin (EQ, 0.5%), or a peroxisome proliferator, clofibrate (CF, 1.0%) or di(2-ethylhexyl)-phthalate (0.3%) and killed at week 16 or 32. The PB promoting regimen was clearly associated with increase in the numbers of high conformity class lesions simultaneously expressing three to five enzymes, and elevated proliferation potential. The inhibitor, EQ, in contrast, brought about a time-dependent decrease in conformity so that only 1 or 2 alterations were most commonly observed at week 32. Lesion populations in the peroxisome proliferator- and especially CF-treated cases were characterized by obvious dissociation between degree of conformity and proliferative status. Such treatment-dependent differences were not always correlated with the size of the lesion. The results thus suggested that the conformity and proliferation potential of preneoplastic lesions are dependent on modification treatment. Overall, GST-P was found to be the most reliable marker, although G6PD was less influenced in the peroxisome proliferator cases.
authors.affiliation: First Department of Pathology, Nagoya City University Medical School.
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: K
authors.initials: K
authors.lastname: Ozaki
authors.forename: S
authors.initials: S
authors.lastname: Uwagawa
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Hakoi
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Ito
mesh_terms: D000251:Adenosine Triphosphatases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004052:Diethylnitrosamine; D005015:Ethoxyquin / Q000494:pharmacology*; D005952:Glucose-6-Phosphatase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D010641:Phenotype; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D007527:Isoenzymes; D004052:Diethylnitrosamine; D005015:Ethoxyquin; D004051:Diethylhexyl Phthalate; D005954:Glucosephosphate Dehydrogenase; D005982:Glutathione Transferase; D005952:Glucose-6-Phosphatase; D000251:Adenosine Triphosphatases; D001973:Bromodeoxyuridine; D002994:Clofibrate; D010634:Phenobarbital