The Effects of diethyl maleate on the N-methyl-N'-nitro-N-nitrosoguanidine induced gastric carcinogenesis in rats

Park, Cheol-bom; Lee, Joon-sup

Korean Journal of Veterinary Research 1995;35(4):793-807.

Cheol-bom Park, Joon-sup Lee

College of Veterinary Medicine, Seoul National University

Diethyl maleate가 N-methyl-N'-nitro-N-nitrosoguanidine에 의해서 유발되는 랫드 위암 발생에 미치는 영향에 관한 병리학적 연구

박철범, 이준섭

서울대학교 수의과대학

Abstract

This study was carried out to investigate the effects of diethyl maleate(DEM) on the carcinogenesis of forestomach and pyloric glandular stomach in rats caused by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). A total of 60 male 6-week-old Wistar rats were given twice intragastric injection of MMNG(200mg/kg BW), then were given diets containing 5% NaCl for 3 weeks until 4th week of the experiment. And then the animals of groups of 1 and 2 were placed on diets containing 0.2% DEM for 16 weeks until the end of 20 weeks of the experiment. On the other hand, the animals of groups of 3 and 4 were placed on basal diets for the same periods. The tissues of forestomach and liver of each group were frozen in liquid nitrogen and the activities of quinone reductase(QR) were determined by measurement of the dicoumarol-sensitive reduction of dichloro-indophenol by NADPH at 600nm. All rats were sacrificed at the end of 20 weeks of the experiment. Every animal was fasted for 24 hrs prior to sacrifice. The forestomach was fixed in 10% neutral phosphate buffered formalin for histology and the pyloric gland was fixed in sublimated formalin for immunohistochemistry of pepsinogen 1 altered pyloric gland(PAPG). The final body weight of the group given MNNG and treated with 5% NaCI and DEM was significantly decreased compared with that of the group 4(p<0.05). Food and water consumption rates were not significantly changed. The preneoplastic and neoplastic lesions of the forestomach given MNNG and treated with 5% NaCI and DEM were significantly increased compared to those of the group 4(p<0.0l). The incidence of PAPG in the groups treated with 0.2% DEM was significantly increased compared with that of the group 4(group 1:p<0.01, group 2:p<0.05). The activities of QR of forestomach in the groups treated with 0.2% DEM were significanitly increased compared with those of the group 4(p<0.001), but those of liver were not significant. These results indicate that DEM exert the enhancing effect of forestomach and glandular stomach carcinogenesis in rats pretreated with MNNG and NaCl.

Key Words: N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), diethyl maleate(DEM), pepsinogen 1 altered pyloric giand(PAPG), quinone reductase(QR)