Significant factors on gastric carcinogenesis revealed by experimental animal models

Masae Tatematsu, Tetsuya Tsukamoto, Tsutomu Mizoshita

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)


The pathological and molecular biochemical analyses in the experimental animal models are important for the solutions of human disorders, including stomach cancer. Stomach cancers are induced experimentally by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) in rats and mice. Helicobacter pylori (H. pylori) is one of the most important factor in the human stomach disorders, and the H. pylori infected and chemical carcinogen treated Mongolian gerbil (MG) has thus proved very useful for the analysis of human stomach carcinogenesis. Intestinal metaplasia is important not as a precancerous lesion but as a paracancerous cord from such studies of clonality of stomach cancers and of phenotypic expression of each intestinal metaplastic or stomach cancer cell, while the pepsinogen altered pyloric glands can be regarded as a common change in rodents, acting as a precursor for a variety of adenocarcinoma types. As the results of the analyses of the MG model, H. pylori is a strong promoter of gastric carcinogenesis rather than an initiator. The dose-dependent enhancing effects of salt on stomach carcinogenesis are demonstrated in the MGs treated with MNU and H. pylori, although high salt intake has a minor influence compared to H. pylori. Bile reflux is not an initiator, but rather an important promoter in the carcinogenesis of gastric stump after partial gastrectomy. Stomach cancers develop from single cells, based on data from clonality analysis in C3H/HeN⇔BALB/c chimeric mice. Intestinalization progresses from gastric, through gastric-and-intestinal mixed, to intestinal phenotypes in non-cancerous and cancerous tissue independently. The chemopreventive effects of H. pylori eradication and reduction of salt intake against stomach cancer are confirmed in the MG models. 2006

Original languageEnglish
Pages (from-to)75-86
Number of pages12
JournalJournal of Toxicologic Pathology
Issue number2
Publication statusPublished - 11-07-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Toxicology


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