Gene-specific oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa.
To study the status of oxidative DNA damage in Helicobacter pylori infection in more detail, we examined oxidative DNA damage to individual genes by determining the loss of PCR product of a targeted gene before and after gastric mucosal DNA was treated with 8-hydroxyguanine glycosylase, which cleaves DNA at the 8-hydroxyguanine residues. The results showed that, of the 5 genes tested, p53, insulin-like growth factor II receptor and transforming growth factor-beta receptor type II showed significant oxidative DNA damage in H. pylori-positive tissues and that the BAX and beta-ACTIN genes were relatively undamaged. These results suggest that in H. pylori infection, oxidative DNA damage does not occur homogeneously throughout the genomic DNA but, rather, in a gene-specific manner. We conclude that the progressive accumulation of preferential oxidative DNA damage in certain genes, such as p53, likely contributes to gastric carcinogenesis.
Choi
Jinhee
J
Department of Pharmacology, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea.
Yoon
Sun-Hee
SH
Kim
Ja-Eun
JE
Rhee
Kwang-Ho
KH
Youn
Hee-Sang
HS
Chung
Myung-Hee
MH
D000328:Adult; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology*; D016158:Genes, p53 / Q000235:genetics; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008297:Male; D009699:N-Glycosyl Hydrolases / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D017527:Receptor, IGF Type 2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics
D017527:Receptor, IGF Type 2; D018125:Receptors, Transforming Growth Factor beta; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D010100:Oxygen