Reduction in oxidatively generated DNA damage following smoking cessation
More details
Hide details
Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
Submission date: 2011-03-03
Acceptance date: 2011-05-12
Publication date: 2011-05-12
Corresponding author
Richard J. O'Connor
Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
Tobacco Induced Diseases 2011;9(May):5
Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.

Participants (n = 19) in this study were recruited from an ongoing 16-week smoking cessation clinical trial and provided blood samples from which leukocyte DNA was extracted and assessed for 3 DNA lesions (thymine glycol modification [d(Tg pA)]; formamide breakdown of pyrimidine bases [d(Tg pA)]; 8-oxo-7,8- dihydroguanine [d(Gh )]) via liquid chromatography tandem mass spectrometry (LC-MS/MS). Change in lesions over time was assessed using generalized estimating equations, controlling for gender, age, and treatment condition.

Overall time effects for the d(Tg pA) (c2 (3) = 8.068, p < 0.045), d(Pf pA) (c2 (3) = 8.477, p < 0.037), and d(Gh ) (c2 (3) = 37.599, p < 0.001) lesions were seen, indicating levels of each decreased significantly after CO-confirmed smoking cessation. The d(Tg pA) and d(Pf pA) lesions show relatively greater rebound at Week 16 compared to the d (Gh ) lesion (88% of baseline for d(Tg pA), 64% of baseline for d(Pf pA), vs 46% of baseline for d(Gh )).

Overall, results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term. Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.

Poulsen HE, Prieme H, Loft S: Role of oxidative DNA damage in cancer initiation and promotion. Eur J Cancer Prev. 1998, 7 (1): 9-16.
Loft S, Poulsen HE: Cancer risk and oxidative DNA damage in man. J Mol Med. 1996, 74 (6): 297-312. 10.1007/BF00207507.
Marnett LJ: Oxyradicals and DNA damage. Carcinogenesis. 2000, 21 (3): 361-70. 10.1093/carcin/21.3.361.
Klaunig JE, Kamendulis LM: The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol. 2004, 44: 239-67. 10.1146/annurev.pharmtox.44.101802.121851.
Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J: Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004, 266 (1-2): 37-56.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007, 39 (1): 44-84. 10.1016/j.biocel.2006.07.001.
Klaunig JE, Kamendulis LM, Hocevar BA: Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol. 2010, 38 (1): 96-109. 10.1177/0192623309356453.
U.S Department of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Health Promotion and Education, Office on Smoking and Health: The Health Consequences of Smoking. Report of the Surgeon General. 2004, Rockville, MD.
Ghosh M, Ionita P: Investigation of free radicals in cigarette mainstream smoke. 3rd Biennial Meeting of the Society for Free Radical Research - Asia (SFRR Asia) & 6th Annual Meeting of the Society for Free Radical Research - India (SFRR India), Lonavala (near Mumbai). 2007, [].
Valavanidis A, Vlachogianni T, Fiotakis K: Tobacco Smoke: Involvement of Reactive Oxygen Species and Stable Free Radicals in Mechanisms of Oxidative Damage, Carcinogenesis and Synergistic Effects with Other Respirable Particles. Int J Environ Res Public Health. 2009, 6: 445-462. 10.3390/ijerph6020445.
Rodgman A, Perfetti TA: The Chemical Components of Tobacco and Tobacco Smoke. 2008, Boca Raton: CRC Press.
Priemé H, Loft S, Klarlund M, Grønbaek K, Tønnesen P, Poulsen HE: Effect of smoking cessation on oxidative DNA modification estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion. Carcinogenesis. 1998, 19 (2): 347-51. 10.1093/carcin/19.2.347.
Lodovici M, Caldini S, Luceri C, Bambi F, Boddi V, Dolara P: Active and passive smoking and lifestyle determinants of 8-oxo-7,8-dihydro-2'-deoxytguanosine levels in human leukocyte DNA. Cancer Epidemiol Biomarkers Prev. 2005, 14: 2975-2877. 10.1158/1055-9965.EPI-04-0906.
Asami S, Manabe H, Miyake J, Tsurudome Y, Hirano T, Yamaguchi R, Itoh H, Kasai H: Cigarette smoking induces an increase in oxidative DNA damage, 8-hydroxydeoxyguanosine, in a central site of the human lung. Carcinogenesis. 1996, 18: 1763-1766.
Besaratinia A, Van Schooten FJ, Schilderman PA, De Kok TM, Haenen GR, Van Herwijnen MH, Van Agen E, Pachen D, Kleinjans JC: A multi-biomarker approach to study the effects of smoking on oxidative DNA damage and repair and antioxidative defense mechanisms. Carcinogenesis. 2001, 21: 395-401.
Van Zeeland AA, de Groot AJ, Halt J, Donato F: 8-Hydroxydeoxyguanosine in DNA from leukocytes of healthy adults: relationship with cigarette smoking, environmental tobacco smoke, alcohol and coffee consumption. Muta Res. 1999, 439: 2490-2570.
Howard DJ, Ota RB, Briggs LA, Hampton M, Pritsos CA: Environmental tobacco smoke in the workplace induces oxidative stress in employees, including increased production of 8-hydroxy-2'-deoxyguanosine. Cancer Epidemiol Biomarkers Prev. 1998, 7 (2): 141-146.
Collier AC, Dandge SD, Woodrow JE, Pritsos CA: Differences in DNA-damage in non-smoking men and women exposed to environmental tobacco smoke (ETS). Toxicol Lett. 2005, 158 (1): 10-19. 10.1016/j.toxlet.2005.02.005.
Cadet J, Berger M, Douki T, Ravanat JL: Oxidative damage to DNA: formation, measurement and biological significance. Rev Physiol Biochem Pharmacol. 1997, 131: 1-87.
Iijima H, Patrzyc HB, Budzinski EE, Dawidzik JB, Freund HG, Box HC: The 1-Carbamoyl-2-oxo-4,5-dihydroxyimidaxoidine component of ROS-induced DNA damage in white blood cells. Radiat Res. 2010, 174: 101-106. 10.1667/RR2087.1.
Iijima H, Patrzyc HB, Budzinski EE, Dawidzik JB, Rodabaugh KJ, Box HC: A study of pyrimidine base damage in relation to oxidative stress and cancer. Brit J Cancer. 2009, 101: 452-456. 10.1038/sj.bjc.6605176.
Bailey DT, DeFedericis HC, Greene KF, Iijima H, Budzinski EE, Patrzyc HB, Dawidzik JB, Box HC: A novel approach to DNA damage assessments: measurement of the thymine glycol lesion. Radiat Res. 2006, 165: 438-444. 10.1667/RR3534.1.
Greene KF, Budzinski EE, Iijima H, Dawidzik JB, DeFedericis HC, Patrzyc HB, Evans MS, Bailey DT, Freund HG, Box HC: Assessment of DNA damage at the dimer level: Measurement of the formamide lesion. Radiat Res. 2007, 167: 146-151. 10.1667/RR0693.1.
Liang KY, Zeger SL: Longitudinal data analysis using generalized linear models. Biometrika. 1986, 73: 13-22. 10.1093/biomet/73.1.13.
Carmella SG, Chen M, Han S, Briggs A, Jensen J, Hatsukami DK, Hecht SS: Effects of smoking cessation on eight urinary tobacco carcinogen and toxicant biomarkers. Toxicology. 2009, 22: 734-741.
Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts LJ: Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers: smoking as a cause of oxidative damage. N Engl J Med. 1995, 332: 1198-1203. 10.1056/NEJM199505043321804.
Campos C, Guzmán R, López-Fernández E, Casado A: Urinary biomarkers of oxidative/nitrosative stress in healthy smokers. Inhal Toxicol. 2011, 23 (3): 148-156. 10.3109/08958378.2011.554460.
Seet RC, Lee CY, Loke WM, Huang SH, Huang H, Looi WF, Chew ES, Quek AM, Lim EC, Halliwell B: Biomarkers of oxidative damage in cigarette smokers: Which biomarkers might reflect acute versus chronic oxidative stress?. Free Radic Biol Med. 2011.
Kocyigit A, Selek S, Celik H, Dikilitas M: Mononuclear leukocyte DNA damage and oxidative stress: The association with smoking of hand-rolled and filter-cigarettes. Mutat Res. 2011, 721 (2): 136-41.
The influence of active and passive smoking during pregnancy on umbilical cord blood levels of vitamins A and E and neonatal anthropometric indices
Olga E. Titova, Elena A. Ayvazova, Fatima A. Bichkaeva, Samantha J. Brooks, Galina N. Chumakova, Helgi B. Schiöth, Christian Benedict
British Journal of Nutrition
Pyrimidine base damage is increased in women with BRCA mutations
Edwin E. Budzinski, Helen B. Patrzyc, Jean B. Dawidzik, Harold G. Freund, Peter Frederick, Heidi E. Godoy, Nicoleta C. Voian, Kunle Odunsi, Harold C. Box
Cancer Letters
Smoking and increased Alzheimer's disease risk: A review of potential mechanisms
Timothy C. Durazzo, Niklas Mattsson, Michael W. Weiner
Alzheimer's & Dementia
Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage
Yang Yu, Yuxiang Cui, Laura J. Niedernhofer, Yinsheng Wang
Chemical Research in Toxicology
Obesity and inflammation markers in relation to leukocyte telomere length in a cross-sectional study of persons with Barrett’s esophagus
Sheetal Hardikar, Xiaoling Song, Rosa Ana Risques, Thomas J. Montine, Catherine Duggan, Patricia L. Blount, Brian J. Reid, Garnet L. Anderson, Mario Kratz, Emily White, Thomas L. Vaughan
BMC Obesity