Ballinger S W, Bouder T G, Davis G S, Judice S A, Nicklas J A, Albertini R J
Genetic Toxicology Laboratory, The University of Vermont College of Medicine, Burlington 05401, USA.
Cancer Res. 1996 Dec 15;56(24):5692-7.
We have investigated the level of mitochondrial DNA (mtDNA) damage and deletions in bronchoalveolar lavage tissues from smokers and nonsmokers using quantitative, extra-long PCR and a "common" mtDNA deletion assay. Smokers had 5.6 times the level of mtDNA damage, 2.6 times the damage at a nuclear locus (beta-globin gene cluster), and almost 7 times the level of a 4.9-kb mtDNA deletion compared to nonsmokers, although the latter increase was not significant. Although both genomes (mitochondrial and nuclear) showed significantly increased levels of DNA damage in smokers (mtDNA P = 0.00072; beta-globin P = 0.0056), the relative differences were greatest in the mtDNA. Damage to the mtDNA may inhibit oxidative phosphorylation and, therefore, potentially cause or contribute to chronic lung disease and cancer. Consequently, the mtDNA may be a sensitive biomarker for environmentally induced genetic damage and mutation.
我们使用定量超长PCR和“常见”线粒体DNA缺失检测方法，研究了吸烟者和非吸烟者支气管肺泡灌洗组织中线粒体DNA（mtDNA）的损伤水平和缺失情况。与非吸烟者相比，吸烟者的mtDNA损伤水平高出5.6倍，核基因座（β-珠蛋白基因簇）处的损伤高出2.6倍，4.9kb mtDNA缺失水平高出近7倍，不过后者的增加并不显著。尽管吸烟者的两个基因组（线粒体和核基因组）的DNA损伤水平均显著升高（mtDNA P = 0.00072；β-珠蛋白P = 0.0056），但mtDNA中的相对差异最大。mtDNA的损伤可能会抑制氧化磷酸化，因此可能导致或促成慢性肺病和癌症。因此，mtDNA可能是环境诱导的基因损伤和突变的敏感生物标志物。
