In this study we investigated whether DNA double-strand breaks (DSBs) contribute to the pathogenesis of COPD.

We immunofluorescence-stained lung tissue samples obtained from COPD patients, asymptomatic smokers, and nonsmokers for markers of DSBs.The numbers of DSB foci (γH2AX, phosphorylated ATM substrate, and phosphorylated 53BP1 foci) per cell in alveolar type I cells, type II cells, and endothelial cells were higher in the COPD patients than in the asymptomatic smokers and nonsmokers. The lung tissue whose type II cells contained higher numbers of γH2AX foci per cell had higher percentages of type II cells that expressed p16, phosphorylated NFκB, and IL-6, and of alveolar wall cells that expressed active caspase-3. The type II cells that contained higher numbers of γH2AX foci per cell had higher rates of expression of p16, phosphorylated NFκB, and IL-6. Half of the alveolar wall cells that expressed active-caspase-3 contained γH2AX foci. Type II cells that stained positive for 8-OHdG contained a higher number of γH2AX foci per cell than the type II cells that stained negative.

In conclusion, DSBs at least in part caused by oxidative stress appear to contribute to the pathogenesis of COPD by inducing apoptosis, cell senescence, and proinflammatory responses.