Inhibition of early-phase exogenous and endogenous liver carcinogenesis intransgenic rats harboring a rat glutathione S-transferase placental form gene

Citation
D. Nakae et al., Inhibition of early-phase exogenous and endogenous liver carcinogenesis intransgenic rats harboring a rat glutathione S-transferase placental form gene, JPN J CANC, 89(11), 1998, pp. 1118-1125
Citations number
57
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
JAPANESE JOURNAL OF CANCER RESEARCH
ISSN journal
0910-5050 → ACNP
Volume
89
Issue
11
Year of publication
1998
Pages
1118 - 1125
Database
ISI
SICI code
0910-5050(199811)89:11<1118:IOEEAE>2.0.ZU;2-N
Abstract
Hepatocarcinogenesis initiated with N-nitrosodiethylamine (DEN) and that in itiated by feeding of a choline-deficient, L-amino acid-defined (CDAA) diet mere compared in transgenic male Wistar rats harboring a rat glutathione S -transferase placental form (GST-P) gene (GST-P-Tg rats) and non-transgenic (N-Tg) rats. Fight-meek-old GST-P-Tg and N-Tg rats were administered DEN i ntraperitoneally at 100 mg/kg body weight, subjected to a selection procedu re with 2-acetylaminofluorene and CCl4, and killed at the end of weeks 5 an d 12. Other groups mere fed the CDAA diet for 12 weeks and killed. Five wee ks after the DEN treatment, numbers and sizes of gamma-glutamyltransferase (GGT)- or GST-P-positive lesions and 8-hydroxyguanine (8-OHG) levels in the livers were significantly less in GST-P-Tg rats than in N-Tg rats. The les ion numbers were unchanged between the ends of weeks 5 and 12 in GST-P-Tg r ats, but decreased in N-Tg rats. The lesion sizes were increased in GST-P-T g rats, but unchanged in N-Tg rats. While the proliferating cell nuclear an tigen labeling indices (PCNA L.I.) in and surrounding the lesions were decr eased, more prominently in GST-P-Tg rats than in N-Tg rats, the 8-OHG level s mere also decreased but similarly in both cases. After 12 weeks on the CD AA diet, the lesion incidences, numbers and sizes, 8-OHG levels, PCNA L.I. in and surrounding the lesions, and liver injury were significantly less in GST-P-Tg rats than in N-Tg rats. These results indicate that insertion of a rat GST-P transgene alters the early phase of exogenous and endogenous ra t hepatocarcinogenesis, presumably due to enhanced detoxification by GST-P expressed both transiently during the initiation and chronically in the alt ered hepatocyte populations.