NNK is a tobacco-specific nitrosamine that has been shown to be an effective pulmonary carcinogen in every animal species tested (15). A total dose of only 6 mg/kg NNK, administered by subcutaneous injection over a period of twenty weeks, induced a significant incidence of lung tumors in rats (16). NNK given in the drinking water to rats at a concentration of 1 ppm for 105 weeks caused a significant incidence of lung tumors, and similar treatment of rats with 5 ppm of NNK or its metabolite NNAL induced lung tumors in more than 85% of the rats (17). A smoker is exposed to an estimated 0.5 mg NNK per kg body weight in 30 years of smoking (18). The major mechanism by which NNK causes lung cancer is through DNA adduct formation resulting in mutations in critical growth control genes, such as K-ras (15). The strong parallels that exist in mechanisms of NNK carcinogenesis between rodents and humans led the International Agency for Research on Cancer to classify NNK as “carcinogenic to humans” (18). Thus, our data indicate that smokers
