Nicotine: Potentially a Multifunctional Carcinogen?

ow nloaded from Cigarette smoking and the use of smokeless chewing tobacco have been closely tied to the development of several human cancers, including lung, oral, esophageal, and bladder. Additionally, individuals exposed to tobacco or tobacco smoke have a substantially increased risk of cardiovascular diseases, destructive periodontitis, and pulmonary, immunological, and gastric dysfunction. Although smoking has been a major public health issue for many decades, a fairly new concern is the use of smokeless chewing tobacco, which is becoming increasingly prevalent among US teenagers and young adult males. Among the most well-characterized chemicals found in tobacco and tobacco smoke are polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene, and the highly addictive alkaloid, nicotine and its metabolites. Traditionally, views of tobacco-related carcinogenesis have been centered on genotoxic mechanisms, i.e. DNA damage/mutation inflicted by the binding of bioactivated and nucleophilic components such as the PAHs. However, with the realization that cancer is a multistep process, requiring many types of chemically-mediated insults, came