Mitochondrial DNA content increase in response to cigarette smoking.
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.
Masayesva
Brett G
BG
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287-0910, USA.
Mambo
Elizabeth
E
Taylor
Rodney J
RJ
Goloubeva
Olga G
OG
Zhou
Shaoyu
S
Cohen
Yoram
Y
Minhas
Khalid
K
Koch
Wayne
W
Sciubba
James
J
Alberg
Anthony J
AJ
Sidransky
David
D
Califano
Joseph
J
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
D000199:Actins; D017931:DNA Primers; D004272:DNA, Mitochondrial; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV