Analysis of p53 mutations and Helicobacter pylori infection in human and animal models.
BACKGROUND
p53 gene mutations are believed to play a critical role in the development of gastric carcinoma. We examined the relation between Helicobacter pylori infection and p53 gene mutations of the gastric mucosa in human and animal models.


METHODS
To detect the original p53 DNA sequences of the Japanese monkey and Mongolian gerbil, the p53 genes of these animals were amplified using the nested polymerase chain reaction method with primers for the human p53 gene. Direct DNA sequencing of exons 5, 6, 7, and 8 of the p53 genes was performed by the dideoxy terminator method for gastric mucosa of humans, the Japanese monkey, and the Mongolian gerbil. The expression of p53 was examined immunohistochemically in a Japanese monkey model.


RESULTS
Mutations of the p53 gene were identified in 52.4% of human H. pylori-positive mucosa and in 100% of monkey H. pylori-positive mucosa. However, no mutations of the p53 gene were found in the H. pylori-positive gastric mucosa of Mongolian gerbils. There were no mutations in H. pylori-negative gastritis mucosa of humans, monkeys, or Mongolian gerbils. Nuclear staining of p53 was seen in the glandular cells of the H. pylori-infected mucosa of Japanese monkeys, especially in the neck region of the glands.


CONCLUSIONS
These findings demonstrate that the H. pylori infection can induce p53 point mutations in humans and the Japanese monkey and appear to be involved in the pathway leading to dysplasia or carcinoma. However, our direct DNA sequencing method showed no p53 mutations in the Mongolian gerbil model at present. Further studies with this model are needed.
Second Department of Internal Medicine, Oita Medical University, Japan.
Kazunari
K
Murakami
Toshio
T
Fujioka
Masaaki
M
Kodama
Shoji
S
Honda
Tadayoshi
T
Okimoto
Touta
T
Oda
Akira
A
Nishizono
Ryugo
R
Sato
Toshihiro
T
Kubota
Jiro
J
Kagawa
Masaru
M
Nasu
D000818:Animals; D002277:Carcinoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D016158:Genes, p53 / Q000235:genetics*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D008251:Macaca; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D013997:Time Factors