Detection of p53 mutations in precancerous gastric tissue.
Intestinal-type gastric cancer is preceded by gastritis and intestinal metaplasia. There is uncertainty regarding the stage at which genetic alterations in the p53 gene occur. Reactive oxygen species (ROS) may participate in the production of mutations and the inactivation of p53 is due to infection by the bacterium Helicobacter pylori. We have investigated whether alterations of the p53 gene can be detected in gastritis and intestinal metaplasia using the restriction site mutation assay. We also assessed the potential contribution of ROS to p53 inactivation using electron spin resonance spectroscopy (ESR) and correlated with the presence of H. pylori. In all, 35% of the gastritis samples and 45% of the intestinal metaplasia samples were found to contain mutations in exons 5-8 of the p53 gene. Electron spin resonance spectroscopy analysis showed a significant increase in free radical levels in gastritis samples compared with normal, intestinal metaplasia and cancer samples, suggesting that free radicals present in gastritis may contribute to p53 mutations. There was no significant difference in free radical levels between the H. pylori-positive and -negative groups. However, a small subpopulation of the H. pylori-negative patients had much higher levels of free radicals. This suggests a more prominent role for other factors in ROS production.
Morgan
C
C
Human Molecular Pathology Group, Swansea Clinical School, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK. claire_morgan70@hotmail.com
Jenkins
G J S
GJ
Ashton
T
T
Griffiths
A P
AP
Baxter
J N
JN
Parry
E M
EM
Parry
J M
JM
D000208:Acute Disease; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D004578:Electron Spin Resonance Spectroscopy; D005753:Gastric Mucosa / Q000473:pathology*; D005756:Gastritis / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D016158:Genes, p53 / Q000235:genetics*; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008679:Metaplasia; D009154:Mutation / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species