Smoking-associated mitochondrial DNA mutations and lipid peroxidation in human lung tissues

To investigate the effect of cigarette smoking on mitochondrial DNA (mtDNA) mutation and lipid peroxidation in lung tissues, 152 samples from lung res ections were collected. A novel deletion of 4,839 bp of mtDNA was found in 80 (52.6%) of the 152 lung samples. The breakpoints of the 4,839-bp mtDNA d eletion were flanked by a nine-nucleotide direct repeat (5'-CATACACAA-3'). The frequency of occurrence and the proportion of the 4,839-bp mtDNA deleti on in the lung increased significantly with the smoking index in terms of p ack-years (P < 0.05). The incidence and proportion of the 4,839-bp mtDNA de letion in the lung tissues of current smokers were significantly higher tha n in those of nonsmokers (P < 0.05). In addition, we found that the content of lipid peroxides in the lung tissues of the smokers was significantly hi gher than in that of nonsmokers, and increased with the smoking index. The average malondialdehyde level in the lung tissues was 12.81 +/- 4.99 mu mol /g for subjects with a smoking index of more than 50 pack-yr, and was 5.39 +/- 0.48 mu mol/g for nonsmokers (P < 0.05). Multiple regression analysis s howed that the smoking index, tissue lipid-peroxide content, and FEV1/FVC r atio were correlated with the proportion of the 4,839-bp mtDNA deletion in the lung. These results suggest that cigarette smoke plays an important rol e in the increase in mtDNA mutation and lipid peroxidation in the lung tiss ues of smokers.