Analysis of p53 mutations and Helicobacter pylori infection in human and animal models

Abstract

Background. p53 gene mutations are believed to play a critical role in the development of gastric carcinoma. We examined the relation betweenHelicobacter pylori infection andp53 gene mutations of the gastric mucosa in human and animal models.Methods. To detect the originalp53 DNA sequences of the Japanese monkey and Mongolian gerbil, thep53 genes of these animals were amplified using the nested polymerase chain reaction method with primers for the humanp53 gene. Direct DNA sequencing of exons 5, 6, 7, and 8 of thep53 genes was performed by the dyedeoxy terminator method for gastric mucosa of humans, the Japanese monkey, and the Mongolian gerbil. The expression ofp53 was examined immunohistochemically in a Japanese monkey model.Results. Mutations of thep53 gene were identified in 52.4% of humanH. pylori-positive mucosa and in 100% of monkeyH. pylori-positive mucosa. However, no mutations of thep53 gene were found in theH. pylori-positive gastric mucosa of Mongolian gerbils. There were no mutations inH. pylori-negative gastritis mucosa of humans, monkeys, or Mongolian gerbils. Nuclear staining of p53 was seen in the glandular cells of theH. pylori-infected mucosa of Japanese monkeys, especially in the neck region of the glands.Conclusions. These findings demonstrate that theH. pylori infection can inducep53 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 nop53 mutations in the Mongolian gerbil model at present. Further studies with this model are needed.