title: Effect of N-Methyl-N-Nitrosourea onHelicobacter-induced Gastric Carcinogenesis in C57BL/6 Mice.
abstract: BACKGROUND
  The aim of this study was to investigate the effect of N-methyl-N-nitrosourea (MNU) treatment followed by chronicHelicobacter pyloriSS1 andH. feliscolonization on the stomachs of C57BL/6 mice. The role of MNU andHelicobacterspecies in gastric carcinogenesis was also elucidated.
  
  
  METHODS
  A total of 69 C57BL/6 mice at 4 weeks of age were divided into 6 groups according to MNU treatment andH. pyloriSS1 orH. felisinfection. The mice were sacrificed at 21 and 50 weeks. The degree of inflammation was determined by histopathology. The levels of gastric mucosal myeloperoxidase, TNF-α, and interleukin-1β (IL-1β) were measured by ELISA.
  
  
  RESULTS
  In theH. felisgroups with or without MNU, the incidence of gastric tumors was 21.1% and 35.0% at 21 and 50 weeks, respectively. No gastric tumors were observed in all control mice. At 50 weeks, 37.5% of gastric adenoma cases were observed in theH. felisalone and MNU +H. felisgroups. Furthermore, 12.5% of gastric adenocarcinoma cases were observed in the MNU alone and MNU +H. felisgroups. The gastric mucosal IL-1β level was significantly higher in the MNU +H. felisgroup at 21 weeks andH. felisgroup at 50 weeks, respectively, than that for control mice (P< 0.05). However, the effect of MNU onH. pyloriSS1-induced gastric carcinogenesis was low compared to that onH. felis.
  
  
  CONCLUSIONS
  Administration of MNU beforeH. felisinfection provokes severe inflammation through IL-1β, and eventually induces gastric cancer. However, the role of MNU inH. pyloriSS1-induced gastric carcinogenesis model is minor.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Ju Yup
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Ryoung Hee
authors.initials: RH
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Yoon Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Seonmin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Daeun
authors.initials: D
authors.lastname: Choi
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
keywords: Gastric neoplasm; Helicobacter felis; Helicobacter pylori; Methylnitrosourea