title: Oxidative DNA damage and somatic mutations: a link to the molecular pathogenesis of chronic inflammatory airway diseases.
abstract: BACKGROUND
  Acquired somatic mutations induced by oxidative stress may contribute to the molecular pathogenesis of chronic inflammatory airway diseases. The objective of this study was to assess the intensity of oxidative DNA damage and the presence of microsatellite DNA instability (MSI), a marker of acquired somatic mutations, in patients with COPD, patients with noncystic fibrosis bronchiectasis, and control subjects.
  
  
  METHODS
  Induced sputum and peripheral blood from 97 subjects were analyzed; 36 patients with COPD, 36 patients with bronchiectasis, 15 smokers without COPD, and 10 healthy control subjects. DNA was extracted and analyzed for MSI. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a specific marker of oxidant-induced DNA damage, was measured in serum and sputum supernatants.
  
  
  RESULTS
  None of the patients with bronchiectasis or control subjects (non-COPD smokers, healthy subjects) exhibited any genetic alteration. In contrast, MSI was found in 38% of COPD specimens. Sputum 8-OHdG was statistically significantly increased in COPD when compared with subjects with bronchiectasis (P = .0002), smokers without COPD (P = .0056), and healthy subjects (P = .0003). Sputum 8-OHdG in MSI-positive patients with COPD differed significantly from that of MSI-negative patients with COPD (P = .04) and smokers without COPD (P = .008), but was not statistically different (P = .07) among MSI-negative patients with COPD and smokers without COPD. Serum 8-OHdG was significantly increased in MSI-positive compared with MSI-negative patients with COPD (P = .001), but was not statistically significant in smokers without COPD (P = .09). Serum 8-OHdG was increased in smokers without COPD compared with MSI-negative patients with COPD (P = .009).
  
  
  CONCLUSIONS
  There is a clear disparity in COPD regarding oxidant-induced DNA damage and somatic mutations. This may reflect a difference in the oxidative stress per se or a deficient antioxidant and/or repair capacity in the lungs of patients with COPD.
authors: Laboratory of Molecular and Cellular Pneumonology, Medical School University of Crete, Greece; Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece. Electronic address: tzortzaki@med.uoc.gr.
authors: Eleni G
authors: EG
authors: Tzortzaki
authors: Sixth Pulmonary Clinic, Chest Hospital "Sotiria," Athens, Greece.
authors: Katerina
authors: K
authors: Dimakou
authors: Laboratory of Molecular and Cellular Pneumonology, Medical School University of Crete, Greece.
authors: Eirini
authors: E
authors: Neofytou
authors: Sixth Pulmonary Clinic, Chest Hospital "Sotiria," Athens, Greece.
authors: Kyriaki
authors: K
authors: Tsikritsaki
authors: Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece.
authors: Katerina
authors: K
authors: Samara
authors: Laboratory of Molecular and Cellular Pneumonology, Medical School University of Crete, Greece.
authors: Maria
authors: M
authors: Avgousti
authors: Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece.
authors: Vassilis
authors: V
authors: Amargianitakis
authors: Laboratory of Molecular and Cellular Pneumonology, Medical School University of Crete, Greece.
authors: Anna
authors: A
authors: Gousiou
authors: Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece.
authors: Sotiris
authors: S
authors: Menikou
authors: Laboratory of Molecular and Cellular Pneumonology, Medical School University of Crete, Greece; Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece.
authors: Nikolaos M
authors: NM
authors: Siafakas
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001987:Bronchiectasis / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry