Role of N-methyl-N-nitrosourea in the induction of intestinal metaplasia and gastric adenocarcinoma in Mongolian gerbils infected with Helicobacter pylori

F. Maruta, H. Ota, R. M. Genta, A. Sugiyama, M. Tatematsu, T. Katsuyama, S. Kawasaki

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background: Progression from intestinal metaplasia to neoplasia has not been demonstrated experimentally. The hypothesis that gastric adenocarcinoma arises from intestinal metaplasia was tested in a Mongolian gerbil model of Helicobacter pylori (H. pylori) infection. Methods: One hundred and fourteen specific pathogen-free gerbils were divided in five groups, A and D: infected with H. pylori and administered the carcinogen N-methyl-N-nitrosourea (MNU); C and E: received MNU; B: H. pylori, but no MNU. Animals were killed at 41 weeks, stomachs were mapped, and the relationship between metaplasia and cancer was assessed. Results: Intestinal metaplasia occurred more frequently in the H. pylori-infected, MNU-treated gerbils than in those receiving H. pylori inoculation only (P < 0.01). Carcinomas arose only in H. pylori-infected animals receiving MNU (8 well differentiated, 2 poorly differentiated, and 10 signet ring). Intestinal metaplasia occurred more frequently in association with intestinal-type carcinoma. Conclusions: Intestinal metaplasia and adenocarcinoma arise in stomachs subjected to the same injuries (in this study, H. pylori and MNU). Only two intestinal-type carcinomas were contiguous to intestinal metaplasia; all other tumors developed most commonly at non-metaplastic sites. This suggests that in this animal model H. pylori and MNU induce several phenotypes of gastric cancer, but intestinal metaplasia may be a direct precursor only in a subset of the intestinal-type tumors.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalScandinavian Journal of Gastroenterology
Volume36
Issue number3
DOIs
StatePublished - Jan 1 2001

Keywords

  • Animal
  • Carcinogenesis
  • Gastric cancer
  • Helicobacter pylori
  • Intestinal metaplasia
  • Mongolian gerbil
  • N-methyl-N-nitrosourea
  • Stomach

ASJC Scopus subject areas

  • Gastroenterology

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