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: Eleni G Tzortzaki, Katerina Dimakou, Eirini Neofytou, Kyriaki Tsikritsaki, Katerina Samara, Maria Avgousti, Vassilis Amargianitakis, Anna Gousiou, Sotiris Menikou, Nikolaos M Siafakas
• Journal: Chest (Chest) Vol. 141 Issue 5 Pg. 1243-1250 (May 2012) ISSN: 1931-3543 [Electronic] United States
• PMID: 22116800 (Publication Type: Journal Article)

Topics

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Bronchiectasis (genetics)
• DNA Damage (genetics)
• DNA Mutational Analysis
• Disease Progression
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Lung Volume Measurements
• Male
• Microsatellite Instability
• Middle Aged
• Oxidative Stress (genetics)
• Pulmonary Disease, Chronic Obstructive (genetics)
• Pulmonary Fibrosis (genetics)
• Reference Values
• Risk Factors
• Smoking (adverse effects)
• Spirometry