Role of N-methyl-N-nitrosourea in the induction of intestinal metaplasia and gastric adenocarcinoma in Mongolian gerbils infected with Helicobacter pylori.
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.
Maruta
F
F
First Dept. of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Ota
H
H
Genta
R M
RM
Sugiyama
A
A
Tatematsu
M
M
Katsuyama
T
T
Kawasaki
S
S
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000473:pathology*; D016480:Helicobacter pylori; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D007414:Intestinal Neoplasms / Q000473:pathology*; D008297:Male; D008770:Methylnitrosourea; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology*; D011336:Probability; D012016:Reference Values; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology*
D008770:Methylnitrosourea