Oxidative DNA damage accumulation in gastric carcinogenesis.
BACKGROUND
Gastric carcinogenesis is a multifactorial, multistep process, in which chronic inflammation plays a major role.


OBJECTIVE
In order to ascertain whether free radical mediated oxidative DNA damage is involved in such a process, concentrations of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TBARS), as an indirect measure of free radical mediated damage, were determined in biopsy specimens from patients undergoing endoscopy.


METHODS
Eighty eight patients were divided into histological subgroups as follows: 27 with chronic non-atrophic gastritis, 41 with atrophic gastritis, six with gastric cancer, and 14 unaffected controls.


METHODS
Intestinal metaplasia, Helicobacter pylori infection, and disease activity were semiquantitatively scored. 8OHdG concentrations were assessed by HPLC with electrochemical detection, and TBARS concentrations were fluorimetrically assayed.


RESULTS
8OHdG concentrations (mean number of adducts/10(5) dG residues) were significantly higher in chronic atrophic gastritis (p = 0.0009). Significantly higher concentrations were also detected in the presence of severe disease activity (p = 0.02), intestinal metaplasia (p = 0.035), and H pylori infection (p = 0.001). TBARS concentrations were also higher in atrophic gastritis, though not significantly so. In a multiple logistic regression analysis, 8OHdG concentrations correlated best with the presence and severity of H pylori infection (r = 0.53, p = 0.002).


CONCLUSIONS
Chronic gastritis is characterised by the accumulation of oxidative DNA damage with mutagenic and carcinogenic potential. H pylori infection is the major determinant for DNA adduct formation.
Farinati
F
F
Cattedra Malattie Apparato Digerente, Universita di Padova, Italy.
Cardin
R
R
Degan
P
P
Rugge
M
M
Mario
F D
FD
Bonvicini
P
P
Naccarato
R
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001205:Ascorbic Acid / Q000032:analysis; D002908:Chronic Disease; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D005750:Gastric Juice / Q000737:chemistry; D005756:Gastritis / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D005773:Gastroscopy; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D012044:Regression Analysis; D013274:Stomach Neoplasms / Q000235:genetics*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D001205:Ascorbic Acid