Possibility of chemoprevention by the eradication of Helicobacter pylori: oxidative DNA damage and apoptosis in H. pylori infection.
OBJECTIVE
The purpose of this study was to study the changes of 8-hydroxydeoxyguanosine (8-OH-dG) contents of DNA from human gastric mucosa with or without Helicobacter pylori and the changes of two biomarkers, iNOS and apoptosis, in gastric biopsies obtained before and after the eradication of H. pylori.


METHODS
DNA isolated from the biopsied human gastric mucosa was digested to deoxynucleotides by nuclease P1, then with Escherichia coli alkaline phosphatase, and analyzed by HPLC-ECD system. 8-OH-dG content was expressed as the number of residues per 10(5) deoxyguanosine. iNOS immunohistochemical staining was performed with antihuman iNOS antiserum generated in mice at a dilution of 1:500, and in situ apoptosis was detected by in situ terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling. Both the density of H. pylori and the degree of inflammation were scored.


RESULTS
The 8-OH-dG contents of healthy normal controls with negative H. pylori were 4.31 +/- 2.33 (8-OH-dG/10(5) dG), whereas those of patients with positive H. pylori were 10.40 +/- 7.25. The difference between these two values was statistically significant (p < 0.01). The 8-OH-dG contents were significantly decreased after the eradication of H. pylori (12.22 +/- 2.09 vs. 2.42 +/- 1.22, p < 0.001). After the eradication of H. pylori, both the apoptotic index and the iNOS scores were significantly decreased, compared with those before eradication (3.72 +/- 1.74 vs. 1.17 +/- 1.06 for apoptosis and 10.34 +/- 6.79 vs. 1.43 +/- 1.14 for iNOS, p < 0.001). Statistically significant correlations were observed among apoptotic index, iNOS score, degree of inflammation, and density of H. pylori (p < 0.05).


CONCLUSIONS
The increased levels of oxidative DNA damage, increased occurrences of apoptosis, and increased expressions of iNOS suggest mechanistic links between H. pylori infection and gastric carcinogenesis.
Hahm
K B
KB
Department of Gastroenterology and Anatomic Pathology, Ajou University School of Medicine, Suwon, Korea.
Lee
K J
KJ
Choi
S Y
SY
Kim
J H
JH
Cho
S W
SW
Yim
H
H
Park
S J
SJ
Chung
M H
MH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology*; D005756:Gastritis / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000382:microbiology / Q000517:prevention & control
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D019001:Nitric Oxide Synthase; D004253:DNA Nucleotidylexotransferase; D003849:Deoxyguanosine