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

被引:21
作者
Nakae, D
Denda, A
Kobayashi, Y
Akai, H
Kishida, H
Tsujiuchi, T
Konishi, Y
Suzuki, T
Muramatsu, M
机构
[1] Nara Med Univ, Ctr Canc, Dept Oncol Pathol, Kashihara, Nara 6348521, Japan
[2] Saitama Med Sch, Dept Biochem, Iruma, Saitama 3500451, Japan
来源
JAPANESE JOURNAL OF CANCER RESEARCH | 1998年 / 89卷 / 11期
关键词
glutathione S-transferase placental form; N-nitrosodiethylamine; choline-deficient; L-amino acid-defined diet; transgenic rat; rat liver carcinogenesis;
D O I
10.1111/j.1349-7006.1998.tb00506.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hepatocarcinogenesis initiated with N-nitrosodiethylamine (DEN) and that initiated 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 intraperitoneally at 100 mg/kg body weight, subjected to a selection procedure with 2-acetylaminofluorene and CCl4, and killed at the end of weeks 5 and 12. Other groups mere fed the CDAA diet for 12 weeks and killed. Five weeks 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 lesion numbers were unchanged between the ends of weeks 5 and 12 in GST-P-Tg rats, but decreased in N-Tg rats. The lesion sizes were increased in GST-P-Tg rats, but unchanged in N-Tg rats. While the proliferating cell nuclear antigen labeling indices (PCNA L.I.) in and surrounding the lesions were decreased, more prominently in GST-P-Tg rats than in N-Tg rats, the 8-OHG levels mere also decreased but similarly in both cases. After 12 weeks on the CDAA 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 rat hepatocarcinogenesis, presumably due to enhanced detoxification by GST-P expressed both transiently during the initiation and chronically in the altered hepatocyte populations.
引用
收藏
页码:1118 / 1125
页数:8
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