DNA and hemoglobin adducts as markers of metabolic activation of tobacco-specific carcinogens

Lung cancer is now the leading cause of excess mortality among smokers in the United States. The ability to identify smokers with the greatest risk of developing lung cancer would be an important step in reducing lung cancer mortality. Tobacco-specific nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N′-nitrosonornicotine are important carcinogens in tobacco smoke. These carcinogens require metabolic activation to exert their carcinogenic effects. Methods are described for the measurement of DNA and hemoglobin adducts formed by the metabolites of these nitrosamines. Preliminary evidence is presented that shows that a subpopulation of smokers have elevated levels of DNA and hemoglobin adducts of tobacco-specific nitrosamines. Further work is in progress to test the hypothesis that smokers with elevated levels of tobacco-specific nitrosamine adducts are at increased risk of developing lung cancer.