Approaches to chemoprevention of lung cancer based on carcinogens in tobacco smoke.

Chemoprevention may be one way to prevent lung cancer in smokers who are motivated to quit but cannot stop. The approach to chemoprevention of lung cancer described in this article is based on an understanding of the lung carcinogens present in tobacco smoke. The available data indicate that the compounds in cigarette smoke most likely involved in the induction of lung cancer in humans are the complex of polynuclear aromatic hydrocarbons typified by benzo[a]pyrene (B[a]P) and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A large number of compounds are now available that inhibit lung tumorigenesis by B[a]P or NNK in rodents. Inhibition of NNK-induced lung carcinogenesis by phenethyl isothiocyanate (PEITC) and inhibition of B[a]P-induced lung carcinogenesis by benzyl isothiocyanate (BITC) are discussed as examples. Studies with PEITC in rodents clearly demonstrate that it inhibits NNK-induced lung tumorigenesis by inhibiting the metabolic activation of NNK. Similar changes appear to occur in humans according to data generated in smokers who ate watercress, a source of PEITC. It is likely that mixtures of chemopreventive agents with activity against carcinogens in tobacco smoke, such as NNK and B[a]P, will be useful in chemoprevention of lung cancer in smokers. Furthermore, there is a need to develop suppressing agents for lung cancer that might be applicable in both smokers and ex-smokers.