title: Mitochondrial DNA content increase in response to cigarette smoking.
abstract: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287-0910, USA.
authors.forename: Brett G
authors.initials: BG
authors.lastname: Masayesva
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mambo
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Taylor
authors.forename: Olga G
authors.initials: OG
authors.lastname: Goloubeva
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Zhou
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Khalid
authors.initials: K
authors.lastname: Minhas
authors.forename: Wayne
authors.initials: W
authors.lastname: Koch
authors.forename: James
authors.initials: J
authors.lastname: Sciubba
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Alberg
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Joseph
authors.initials: J
authors.lastname: Califano
mesh_terms: D000199:Actins / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D003430:Cross-Sectional Studies; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012044:Regression Analysis; D012463:Saliva; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D016540:Smoking Cessation
chemical_list: D000199:Actins; D017931:DNA Primers; D004272:DNA, Mitochondrial; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV