Long-term Helicobacter pylori infection in Japanese monkeys induces atrophic gastritis and accumulation of mutations in the p53 tumor suppressor gene.
BACKGROUND
Helicobacter pylori is accepted as a definite human gastric carcinogen from an epidemiological point of view despite insufficient experimental data. Although we previously showed that the number of p53 immunopositive cells in the atrophic gastric mucosa of H. pylori-infected Japanese monkeys gradually increased over time, data on p53 gene mutations were not obtained in that study. To obtain direct evidence of carcinogenesis associated with H. pylori infection, we investigated whether p53 gene mutations are present in the gastric mucosa of a nonhuman primate model susceptible to H. pylori.


METHODS
Using the DNA from gastric tissues obtained from six H. pylori-uninfected monkeys of different ages, nucleotide sequence of the wild-type p53 gene was determined by amplification of exons (Ex) 5, 6, 7 and 8 and sequencing. Gastric specimens obtained from eight Japanese monkeys that had been infected with H. pylori for different lengths of time (1.5-7.5 years), were analyzed for mutations in exons 5-8 of p53.


RESULTS
In the six H. pylori-uninfected monkeys, nucleotide sequences of p53 Ex 5-8 were completely common and no mutations were noted. However, among the monkeys that were infected with H. pylori over various periods of time, there was an accumulation of p53 nucleotide (amino acid) substitutions as the gastric atrophy score increased.


CONCLUSIONS
We conclude that the appearance of p53 gene mutation may be closely associated with the degree of gastric mucosal atrophy, which depends on the duration of H. pylori infection. Searching for p53 gene mutations may be useful for studying the progression of gastric carcinogenesis associated with H. pylori.
Oda
Touta
T
Second Department of Internal Medicine, Oita Medical University, Hasama-machi, Japan.
Murakami
Kazunari
K
Nishizono
Akira
A
Kodama
Masaaki
M
Nasu
Masaru
M
Fujioka
Toshio
T
D000818:Animals; D001483:Base Sequence; D005091:Exons; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005757:Gastritis, Atrophic / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D000882:Haplorhini; D016481:Helicobacter Infections / Q000235:genetics / Q000473:pathology*; D016480:Helicobacter pylori; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53