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To investigate the effect of cigarette smoking on mitochondrial DNA (mtDNA) mutation and lipid peroxidation in lung tissues, 152 samples from lung resections 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 deletion were flanked by a nine-nucleotide direct repeat (5'-CATACACAA-3'). The frequency of occurrence and the proportion of the 4,839-bp mtDNA deletion in the lung increased significantly with the smoking index in terms of pack-years (P < 0.05). The incidence and proportion of the 4,839-bp mtDNA deletion in the lung tissues of current smokers were significantly higher than 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 higher than in that of nonsmokers, and increased with the smoking index. The average malondialdehyde level in the lung tissues was 12.81+/- 4.99 q,mol/g for subjects with a smoking index of more than 50 packyr, and was 5.39 +/- 0.48 wmol/g for nonsmokers (P < 0.05). Multiple regression analysis showed that the smoking index, tissue lipid-peroxide content, and FEV^sub 1^/FVC ratio were correlated with the proportion of the 4,839-bp mtDNA deletion in the lung. These results suggest that cigarette smoke plays an important role in the increase in mtDNA mutation and lipid peroxidation in the lung tissues of smokers. Fahn, H.-J., L.-S. Wang, S.-H. Kao, S.-C. Chang, M.-H. Huang, and Y.-H. Wei. 1998. Smoking-associated mitochondrial DNA mutations and lipid peroxidation in human lung tissues. Am. J. Respir. Cell Mol. Biol. 19:901-909.
Abbreviations: butylated hydroxytoluene, BHT; mitochondrial DNA, mtDNA; malondialdehyde, MDA; oxidative phosphorylation, OXPHOS; polymerase chain reaction, PCR; thiobarbituric acid, TBA.
Cigarette smoke is a complex mixture of more than 3,800 compounds, including both free radicals in high concentrations and chemical compounds that readily react to form other reactive substances (1-3). Mainstream and sidestream gas-phase cigarette smoke each contain about the same concentration of about 1 x 10^sup 16^ free radicals per cigarette (or 5 x 10^sup 14^ free radicals per puff) (3). These free radicals are reactive yet remarkably long-lived in gasphase smoke, lasting for more than 5 min. They may randomly attack various cellular constituents and thereby impair some...