Everyday Toxicology II: Tobacco

  • Philip C. Burcham


The chemical complexity of tobacco combustion ensures smokers daily inhale a toxic cocktail comprising thousands of xenobiotics. Unsurprisingly, many health disorders accompany this habit including various cancers plus noncancer conditions such as emphysema. The smoke constituents causing lung injury have received much attention, with special interest focussed on carcinogens that drive the induction and progression of lung cancer. Major carcinogens within tobacco smoke include the polycyclic aromatic hydrocarbons, nitrosamines, aromatic amines and volatile organics such as 1,3-butadiene. Due to their strong carcinogenic potency, the tobacco-specific nitrosamines NNN and NNK are of particular concern. Both form via nitrosation of nicotine, the neurostimulatory Nicotiana constituent that confers the highly addictive properties upon cigarette smoke. As with other tobacco smoke carcinogens, NNN and NNK undergo CYP-catalysed bioactivation to DNA-damaging metabolites. DNA adducts formed by these and other noxious metabolites drive the accumulation of mutations in growth regulatory genes within the smokers’ lung.


Aromatic amines Benzo[a]pyrene 1,3-Butadiene Chronic obstructive pulmonary disease Free radicals Irritants Lung cancer Metals Microarrays Tobacco production Tobacco combustion Tar 

Going Further

  1. Baird WM et al. Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action. Environ Mol Mutagen. 2005;45:106–14.PubMedCrossRefGoogle Scholar
  2. Besaratinia A, Tommasi S. Genotoxicity of tobacco smoke-derived aromatic amines and bladder cancer: current state of knowledge and future research directions. FASEB J. 2013;27:2090–100.PubMedCrossRefGoogle Scholar
  3. Boyle JO et al. Effects of cigarette smoke on the human oral mucosal transcriptome. Cancer Prev Res (Phila). 2010;3:266–78.CrossRefGoogle Scholar
  4. Carmella SG et al. Effects of smoking cessation on eight urinary tobacco carcinogen and toxicant biomarkers. Chem Res Toxicol. 2009;22:734–41.PubMedCrossRefGoogle Scholar
  5. Decramer M et al. Chronic obstructive pulmonary disease. Lancet. 2012;379:1341–51.PubMedCrossRefGoogle Scholar
  6. Doll R, Peto R. Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers. J Epidemiol Community Health. 1978;32:303–13.PubMedCrossRefGoogle Scholar
  7. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst. 1981;66:1191–308.PubMedGoogle Scholar
  8. Dunbar A et al. Second-hand tobacco smoke and cardiovascular disease risk: an epidemiological review. Cardiol Rev. 2013;21:94–100.PubMedCrossRefGoogle Scholar
  9. Fowles J, Dybing E. Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke. Tob Control. 2003;12:424–30.PubMedCrossRefGoogle Scholar
  10. Ghio AJ et al. Particulate matter in cigarette smoke alters iron homeostasis to produce a biological effect. Am J Respir Crit Care Med. 2008;178:1130–8.PubMedCrossRefGoogle Scholar
  11. Giovino GA. The tobacco epidemic in the United States. Am J Prev Med. 2007;33(Suppl):S318–26.PubMedCrossRefGoogle Scholar
  12. Glynn T et al. The globalization of tobacco use: 21 challenges for the 21st century. CA Cancer J Clin. 2010;60:50–61.PubMedCrossRefGoogle Scholar
  13. Haussmann HJ. Use of hazard indices for a theoretical evaluation of cigarette smoke composition. Chem Res Toxicol. 2012;25:794–810.PubMedCrossRefGoogle Scholar
  14. Hecht SS. More than 500 trillion molecules of strong carcinogens per cigarette: use in product labeling? Tob Control. 2011;20:387.PubMedCrossRefGoogle Scholar
  15. Hecht SS. Lung carcinogenesis by tobacco smoke. Int J Cancer. 2012;131:2724–32.PubMedCrossRefGoogle Scholar
  16. Henkler F et al. Exposure to polycyclic aromatic hydrocarbons: bulky DNA adducts and cellular responses. EXS. 2012;101:107–31.PubMedGoogle Scholar
  17. Kasiviswanathan R et al. Translesion synthesis past acrolein-derived DNA adducts by human mitochondrial DNA polymerase γ. J Biol Chem. 2013;288:14247–55.PubMedCrossRefGoogle Scholar
  18. Kim SI et al. New experimental data linking secondhand smoke exposure to lung cancer in nonsmokers. FASEB J. 2012;26:1845–54.PubMedCrossRefGoogle Scholar
  19. Lewis GP et al. Contribution of cigarette smoking to cadmium accumulation in man. Lancet. 1972;299:291–2.CrossRefGoogle Scholar
  20. McGrath TE et al. Formation of polycyclic aromatic hydrocarbons from tobacco: the link between low temperature residual solid (char) and PAH formation. Food Chem Toxicol. 2007;45:1039–50.PubMedCrossRefGoogle Scholar
  21. Pappas RS. Toxic elements in tobacco and in cigarette smoke: inflammation and sensitization. Metallomics. 2011;3:1181–98.PubMedCrossRefGoogle Scholar
  22. Pinkerton KE et al. Distribution of particulate matter and tissue remodeling in the human lung. Environ Health Perspect. 2000;108:1063–9.PubMedCrossRefGoogle Scholar
  23. Spiess PC et al. Proteomic profiling of acrolein adducts in human lung epithelial cells. J Proteomics. 2011;74:2380–94.PubMedCrossRefGoogle Scholar
  24. Thompson CA, Burcham PC. Genome-wide transcriptional responses to acrolein. Chem Res Toxicol. 2008;21:2245–56.PubMedCrossRefGoogle Scholar
  25. Turesky RJ, Le Marchand L. Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines. Chem Res Toxicol. 2011;24:1169–214.PubMedCrossRefGoogle Scholar
  26. Willis DN et al. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. FASEB J. 2011;25:4434–44.PubMedCrossRefGoogle Scholar
  27. Yauk CL et al. Genetic toxicology and toxicogenomic analysis of three cigarette smoke condensates in vitro reveals few differences among full-flavor, blonde, and light products. Environ Mol Mutagen. 2012;53:281–96.PubMedCrossRefGoogle Scholar
  28. Yoon JI et al. Organ specificity of the bladder carcinogen 4-aminobiphenyl in inducing DNA damage and mutation in mice. Cancer Prev Res (Phila). 2012;5:299–308.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Philip C. Burcham
    • 1
  1. 1.School of Medicine and PharmacologyThe University of Western AustraliaPerthAustralia

Personalised recommendations