The effect of Helicobacter pylori infection on levels of DNA damage in gastric epithelial cells.
BACKGROUND
Helicobacter pylori infection leads to an increased risk of developing gastric cancer. The mechanism through which this occurs is not known. We aimed to determine the effect of H. pylori and gastritis on levels of DNA damage in gastric epithelial cells.


METHODS
Epithelial cells were isolated from antral biopsies from 111 patients. DNA damage was determined using single cell gel electrophoresis and the proportion of cells with damage calculated before and 6 weeks after eradication of H. pylori. Cell suspensions generated by sequential digestions of the same biopsies were assayed to determine the effect of cell position within the gastric pit on DNA damage.


RESULTS
DNA damage was significantly higher in normal gastric mucosa than in H. pylori gastritis [median (interquartile range) 65% (58.5-75.8), n = 18 and 21% (11.9-29.8), n = 65, respectively, p <.001]. Intermediate levels were found in reactive gastritis [55.5% (41.3-71.7), n = 13] and H. pylori negative chronic gastritis [50.5% (36.3-60.0), n = 15]. DNA damage rose 6 weeks after successful eradication of H. pylori[to 39.5% (26.3-51.0), p =.007] but was still lower than in normal mucosa. Chronic inflammation was the most important histological factor that determined DNA damage. DNA damage fell with increasing digestion times (r = -.92 and -.88 for normal mucosa and H. pylori gastritis, respectively).


CONCLUSIONS
Lower levels of DNA damage in cells isolated from H. pylori infected gastric biopsies may be a reflection of increased cell turnover in H. pylori gastritis. The investigation of mature gastric epithelial cells for DNA damage is unlikely to elucidate the mechanisms underlying gastric carcinogenesis.
Everett
S M
SM
The Centre for Digestive Diseases, The General Infirmary at Leeds, Great George Street, Leeds, LS1 3EX, UK.
White
K L M
KL
Drake
I M
IM
Schorah
C J
CJ
Calvert
R J
RJ
Skinner
C
C
Stringer
M D
MD
Miller
D
D
Dixon
M F
MF
Chalmers
D M
DM
Axon
A T R
AT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D020552:Comet Assay; D004249:DNA Damage; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology*; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology*; D005756:Gastritis / Q000382:microbiology / Q000473:pathology*; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged