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Oxidative DNA damage accumulation in gastric carcinogenesis
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  1. F Farinatia,
  2. R Cardina,
  3. P Deganc,
  4. M Rugged,
  5. F Di Marioa,
  6. P Bonvicinib,
  7. R Naccaratoa
  1. aCattedra Malattie Apparato Digerente, Istituto Medicina Interna, bCattedra Biochimica Clinica, Istituto Medicina di Laboratorio, Universita di Padova, Italy, cIstituto Nazionale per la Ricerca sul Cancro, Genova, Italy, dCattedra di Istochimica ed Immuno Istochimica Patologica, Istituto di Anatomia Patologica, Italy
  1. Dr F Farinati, Cattedra Malattie Apparato Digerente, Istituto Medicina Interna, Policlinico Universitario, Via Giustiniani 2, 35128 Padova, Italy.

Abstract

Background—Gastric carcinogenesis is a multifactorial, multistep process, in which chronic inflammation plays a major role.

Aims—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.

Patients—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/105 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.

  • free radicals
  • oxidative DNA damage
  • gastric carcinogenesis
  • precancerous changes
  • peroxidative damage

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