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Oxidative DNA Damage and Somatic Mutations: a link to the molecular pathogenesis of Chronic Inflammatory Airway Diseases.
MedLine Citation:
PMID:  22116800     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ABSTRACT BACKGROUND:Acquired somatic mutations induced by oxidative stress may contribute to the molecular pathogenesis of chronic inflammatory airway diseases. OBJECTIVES: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 chronic obstructive pulmonary disease (COPD), in patients with non-cystic fibrosis bronchiectasis, and in controls. METHODS:Induced sputum and peripheral blood from 97 subjects were analyzed; 36 COPD patients, 36 bronchiectasis patients, 15 non-COPD smokers and 10 healthy controls. DNA was extracted and analyzed for MSI. 8-OHdG, a specific marker of oxidant-induced DNA damage was measured in serum and sputum supernatants. RESULTS:Neither of the bronchiectasis patients nor controls (non-COPD smokers, healthy subjects) exhibited any genetic alteration. In contrast, MSI was found in 38% of COPD specimens. Sputum 8-OHdG was statistically significant increased in COPD when compared with bronchiectasis (p=0.0002), with non-COPD smokers (p=0.0056) and healthy subjects (p=0.0003). Sputum 8-OHdG in MSI-positive COPD patients differed significantly from MSI-negative COPD patients (p=0.04) and non-COPD smokers (p=0.008), but not statistically different (p=0.07) among MSI-negative COPD patients and non-COPD smokers. Serum 8-OHdG was significantly increased in MSI-positive compared with MSI-negative COPD patients, (p=0.001) but not statistically significant in non-COPD smokers (p=0.09). Serum 8-OHdG was increased in non-COPD smokers versus MSI-negative COPD patients (p=0.009). 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 COPD patients.
Authors:
Eleni G Tzortzaki; Katerina Dimakou; Eirini Neofytou; Kyriaki Tsikritsaki; Katerina Samara; Maria Avgousti; Vassilis Amargianitakis; Anna Gousiou; Sotiris Menikou; Nikolaos M Siafakas
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-23
Journal Detail:
Title:  Chest     Volume:  -     ISSN:  1931-3543     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Laboratory of Molecular and Cellular Pneumonology, Medical School University of Crete, Greece;
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