title: Possible tumor development from double positive foci for TGF-alpha and GST-P observed in early stages on rat hepatocarcinogenesis.
abstract: Expression of TGF-alpha during promotion of neoplastic development from GST-P-positive foci in rat chemical hepatocarcinogenesis was investigated. One-hundred male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg bodyweight) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, PB at doses of 0 or 500 p.p.m. was fed to the rats for 46 weeks. Groups of 10 rats were killed at weeks 4, 8, 16, 32, 48 and their livers were immunohistochemically examined for expression of GST-P and TGF-alpha. TGF-alpha-positive foci and single positive cells were observed from week 4, partially overlapping with GST-P-positive foci but being much fewer. Numbers of TGF-alpha-positive lesions did not increase from weeks 4-48, but their areas showed increment at weeks 32 and 48, especially with PB administration. Almost all of the tumors observed at weeks 16, 32 and 48 were positive for TGF-alpha (98%). In addition, epidermal growth factor receptor overexpression was observed in most TGF-alpha-positive lesions (foci and tumors). The proliferating cell nuclear antigen labeling index in double positive foci for GST-P and TGF-alpha was significantly higher than that in TGF-alpha-negative foci. In conclusion, TGF-alpha may be closely related with promotion from altered foci to neoplasms in rat hepatocarcinogenesis. Our data suggest that double positive foci for GST-P and TGF-alpha in the early stages of rat hepatocarcinogenesis may develop into tumors with promotion.
authors.affiliation: First Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Osaka 545-8585, Japan. mitsuaki_kitano@kn.kaneka.co.jp
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Kitano
authors.forename: Jutaro
authors.initials: J
authors.lastname: Wada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ariki
authors.forename: Masanori
authors.initials: M
authors.lastname: Kato
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Morimura
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Hidaka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hosoe
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D004052:Diethylnitrosamine / Q000633:toxicity; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006498:Hepatectomy; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D010634:Phenobarbital / Q000633:toxicity; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D016211:Transforming Growth Factor alpha; D004052:Diethylnitrosamine; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat; D010634:Phenobarbital