Assessment of the degree of DNA damage in leukocytes of patients with chronic obstructive pulmonary disease

Introduction. Oxidative stress plays a key role in the pathogenesis of COPD. Cigarette smoke induces oxidative stress, which causes DNA damage in cells. Transient receptor potential (TRP) channels are capable of mediating the effects of tobacco smoke and reactive oxygen species.

Aim. Studying the level of H2AX histones phosphorylation (γH2AX) indicating DNA damage in leukocytes of COPD patients and establishing its relationship with TRPV1 and 

TRPV4 expression.

Materials and methods. The study included 47 patients with COPD of varying severity and 25 controls. All subjects underwent spirometry to assess lung function. Histone H2AX phosphorylation and TRPV1/TRPV4 expression on leukocytes were determined by flow cytometry. Spearman's rank correlation coefficient (ρ) was used to search for relationships between quantitative variables.

Results. Lymphocytes of COPD patients were characterized by higher level of γH2AX (%) than lymphocytes from the controls (p=0.04). Lymphocytes of smokers also showed a greater degree of DNA damage as compared to healthy non-smokers (p=0.02). Significant differences were observed when comparing γH2AX expression (%) between COPD patients and healthy non-smokers in lymphocytes (p=0.001) and monocytes (p=0.04). Smoking more than 20 pack-years was associated with higher γH2AX (%) in lymphocytes (p=0.04) of COPD patients. Expression of TRPV1 and γH2AX (%) showed significant correlations on granulocytes (ρ=0.76, p<0.001), lymphocytes (ρ=0.34, p=0.03) and monocytes (ρ=0.55, p<0.001).

Conclusion. COPD patients differ from the control group by more pronounced DNA damage, which is most evident in lymphocytes. Smoking is a factor that negatively affects the formation of DNA breaks. TRPV1 expression may play a role in oxidative DNA damage in leukocytes by increasing the production of reactive oxygen species.

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