title: Role of bacterial strain diversity of Helicobacter pylori in gastric carcinogenesis induced by N-methyl-N-nitrosourea in Mongolian gerbils.
abstract: OBJECTIVE
  Helicobacter pylori is known to enhance gastric carcinogenesis induced by chemical carcinogens. We previously demonstrated that infection with H. pylori strain SS1 did not enhance such carcinogenesis in C57BL/6 mice. Whether this result was due to the bacterial strain SS1 or to the experimental host, C57BL/6 mice, should be addressed. Therefore, we examined whether H. pylori strains introduced to the same host (Mongolian gerbils) differed in carcinogenicity.
  
  
  METHODS
  H. pylori TN2GF4 strain (CagA(+), VacA(+)) and SS1 strain (CagA functionally(-), VacA(-)) were infected to Mongolian gerbils (n = 126). In the first experiment (induction of gastritis), histologic change in gastric mucosa of gerbils infected by H. pylori (TN2GF4, SS1, vehicle) without N-methyl-N-nitrosourea (MNU) at 1 month or 6 months was assessed. In the second experiment (experimental carcinogenesis), H. pylori (TN2GF4, SS1, vehicle) was inoculated to the gerbils after administration of MNU for 10 weeks, and the number of cancers and histopathologic changes at week 54 were assessed.
  
  
  RESULTS
  In the first experiment, activity and inflammation in the TN2GF4 group were significantly greater than in the SS1 group at 1 month, while no significant difference was noted at 6 months. On the other hand, intestinal metaplasia and atrophy were significantly greater with TN2GF4 than with SS1 at 6 months but not at 1 month. In studies on experimental carcinogenesis, microscopically, 47.8% (11/23), 26% (7/26), and 0% (0/26), of animals had gastric adenocarcinoma in the MNU + TN2GF4 group, MNU + SS1 group, and MNU alone group, respectively.
  
  
  CONCLUSIONS
  Both H. pylori strains, TN2GF4 and SS1, promoted carcinogenesis in Mongolian gerbils. The severity of gastritis and destruction and restoration of gastric mucosa may be related to gastric carcinogenesis. That the SS1 strain significantly accelerated carcinogenesis only in Mongolian gerbils and not in C57BL/6 mice suggests the crucial role of host factors in carcinogenesis by H. pylori infection.
authors.affiliation: Division of Upper Gastroenterology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Tomotaro
authors.initials: T
authors.lastname: Kawazoe
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakagami
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakajima
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Hori
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced*; D000818:Animals; D015197:Carcinogenicity Tests; D004195:Disease Models, Animal; D005756:Gastritis; D005849:Gerbillinae; D016480:Helicobacter pylori / Q000737:chemistry* / Q000145:classification; D008770:Methylnitrosourea; D051379:Mice; D008810:Mice, Inbred C57BL; D013274:Stomach Neoplasms / Q000139:chemically induced*
chemical_list: D008770:Methylnitrosourea