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Carcinogenesis Advance Access originally published online on February 14, 2008
Carcinogenesis 2008 29(6):1170-1177; doi:10.1093/carcin/bgn034
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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Associations between cigarette smoking and mitochondrial DNA abnormalities in buccal cells

Duanjun Tan, David S. Goerlitz, Ramona G. Dumitrescu, Dingfen Han, Françoise Seillier-Moiseiwitsch, Stephanie M. Spernak, Roy Anthony Orden, Jinguo Chen, Radoslav Goldman and Peter G. Shields*

Cancer Genetics and Epidemiology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA

* To whom correspondence should be addressed. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Reservoir Road Northwest, LL Level, Room 150, PO Box 571465, Washington, DC 20057, USA. Tel: +1 202 687 0003; Fax: +1 202 687 0004; Email: pgs2{at}georgetown.edu

DNA alterations in mitochondria are believed to play a role in carcinogenesis and are found in smoking-related cancers. We sought to replicate earlier findings for the association of smoking with increased mitochondrial DNA (mtDNA) content in buccal cells and further hypothesized that there would be an increased number of somatic mtDNA mutations in smokers. Buccal cells and blood lymphocytes were studied from 42 healthy smokers and 30 non-smokers. Temporal temperature gradient electrophoresis screening and sequencing was used to identify mtDNA mutations. The relative mtDNA content was determined by real-time polymerase chain reaction. Assuming that mtDNA in lymphocytes represents the inherited sequence, it was found that 31% of smokers harbored at least one somatic mtDNA mutation in buccal cells with a total of 39 point mutations and 8 short deletions/insertions. In contrast, only 23% of non-smokers possessed mutations with a total of 10 point mutations and no insertions/deletions detected. mtDNA somatic mutation density was higher in smokers (0.68/10 000 bp per person) than in non-smokers (0.2/10 000 bp per person). There was a statistically significant difference in the pattern of homoplasmy and heteroplasmy mutation changes between smokers and non-smokers. Whereas non-smokers had the most mutations in D-loop region (70%), smokers had mutations in both messenger RNA encoding gene (36%) and D-loop region (49%). The mean ratio of buccal cells to lymphocytes of mtDNA content in smokers was increased (2.81) when compared with non-smokers (0.46). These results indicate that cigarette smoke exposure affects mtDNA in buccal cells of smokers. Additional studies are needed to determine if mitochondrial mutation assays provide new or complementary information for estimating cigarette smoke exposure at the cellular level or as a cancer risk biomarker.

Abbreviations: Co, cytochrome c oxidase; HT, heteroplasmy; HM, homoplasmy; mtDNA, mitochondrial DNA; PCR, polymerase chain reaction; ROS, reactive oxygen species; TTGE, temporal temperature gradient electrophoresis

Received October 11, 2007; revised January 22, 2008; accepted January 28, 2008.


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