Carcinogenic Effects of Cigarette Smoke on the Respiratory Tract*

Abstract

Cigarette smoking is the major cause of lung cancer in the United States and worldwide. Tobacco products are estimated to cause approximately 90% of lung cancer cases. Experimental studies in laboratory animals have collectively demonstrated the carcinogenicity of cigarette smoke and cigarette smoke condensates (CSCs). There are over 5000 identified chemicals and more than 60 known carcinogens in cigarette smoke, with polycyclic aromatic hydrocarbons (PAHs) and the tobacco-specific nitrosamine NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) likely being the most important respiratory carcinogens. The carcinogenicity of cigarette smoke can also be enhanced by the presence of tumor promoters and cocarcinogens. The reaction of carcinogens with DNA can cause mutations and, if unrepaired, can lead to the activation of oncogenes or the inactivation of tumor suppressors. Epigenetic changes may also occur from exposure to tobacco carcinogens, leading to a change in gene expression. While the majority of lung cancer results from cigarette smoking, only 15% of smokers get lung cancer. Studies indicate that this may be due to genetic factors that contribute to a person’s susceptibility to tobacco-induced cancers. Biomarkers have been developed to monitor uptake and activation of tobacco carcinogens, and perhaps could be used to predict susceptibility to lung cancer. Chemoprevention has developed as an approach to prevent or delay the onset of tobacco-induced lung caner. However, cessation of tobacco products is the best way to prevent lung cancer.