Mitochondrial DNA content increase in response to cigarette smoking
Mitochondrial DNA content increase in response to cigarette smoking
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DOI：
10.1158/1055-9965.epi-05-0210
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发表时间：
2006-01-01
影响因子：
3.8
通讯作者：
Califano, J
中科院分区：
文献类型：
--
作者：
Masayesva, BG;Mambo, E;Califano, J
线粒体DNA(MtDNA)含量的增加和线粒体功能的下降随着年龄的增长和对包括烟草烟雾在内的DNA损伤剂的反应而发生。我们进行了一项横断面研究，并量化了不同吸烟和酒精暴露人群中线粒体DNA含量的变化。对参与吸烟相关上呼吸道恶性肿瘤筛查研究的604名个体的年龄、吸烟史、酒精摄入量和其他人口统计学数据进行了表征。从唾液脱落细胞中提取总DNA。核蛋白基因β-肌动蛋白和两个线粒体基因细胞色素C氧化酶I和II(COX I和COX II)的DNA通过实时定量聚合酶链式反应进行定量。通过多元回归分析，线粒体DNA含量与年龄、暴露史和其他变量相关。与从不吸烟者相比，吸烟者(COX I和COX II分别增加31%和29%)和既往吸烟者(31%和34%)线粒体DNA含量显著增加(P<；0.001)。在调整了包括年龄、饮酒和收入在内的其他重要因素后，这种关联仍然存在(P<；0.001)。线粒体DNA含量升高与吸烟年限呈正相关(P=0.02)。尽管既往吸烟者的平均戒烟间隔为21年，但戒烟间隔与mtDNA含量在统计学上没有显著相关性。吸烟与线粒体DNA含量的增加呈剂量依赖关系。在戒烟后，线粒体DNA对吸烟的反应持续了几十年，这与长期的吸烟相关损害是一致的。
An increase in mitochondrial DNA (mtDNA) content and decline in mitochondrial function occurs with aging and in response to DNA-damaging agents, including tobacco smoke. We did a cross-sectional study and quantified changes in mtDNA content in a population of individuals with varied smoking and alcohol exposure. Age, smoking history, ethanol intake, and other demographic data were characterized for 604 individuals participating in a screening study for smoking-related upper aerodigestive malignancy. Total DNA was extracted from exfoliated cells in saliva. DNA from a nuclear gene, beta-actin, and two mitochondrial genes, cytochrome c oxidase I and II (Cox I and Cox II), were quantified by real-time PCR. mtDNA content was correlated with age, exposure history, and other variables using multivariate regression analyses. A significant increase (P < 0.001) in mtDNA content was noted in smokers (31% and 29% increase for Cox I and Cox II, respectively) and former smokers (31% and 34%) when compared with never smokers. This association persisted after adjustment for other significant factors including age, alcohol drinking, and income (P < 0.001). Increased mtDNA content was positively associated with pack-years of smoking (P = 0.02). Despite an average smoking cessation interval of 21 years in former smokers, tobacco cessation interval was not statistically significantly associated with mtDNA content. Smoking is associated with increased mtDNA content in a dose-dependent fashion. Mitochondrial DNA alterations in response to smoking persist for several decades after smoking cessation, consistent with long-term, smoking-related damage.