| Oxidative DNA Damage and Somatic Mutations: a link to the molecular pathogenesis of Chronic Inflammatory Airway Diseases. | |
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MedLine Citation:
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PMID: 22116800 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Eleni G Tzortzaki; Katerina Dimakou; Eirini Neofytou; Kyriaki Tsikritsaki; Katerina Samara; Maria Avgousti; Vassilis Amargianitakis; Anna Gousiou; Sotiris Menikou; Nikolaos M Siafakas |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-23 |
Journal Detail:
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Title: Chest Volume: - ISSN: 1931-3543 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0231335 Medline TA: Chest Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Laboratory of Molecular and Cellular Pneumonology, Medical School University of Crete, Greece; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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