APPROACHES TO CHEMOPREVENTION OF LUNG-CANCER BASED ON CARCINOGENS IN TOBACCO-SMOKE

Chemoprevention may be one way to prevent lung cancer in smokers who a re motivated to quit but cannot stop. The approach to chemoprevention of lung cancer described in this article is based on an understanding of the rung carcinogens present in tobacco smoke. The available data i ndicate 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 tobac co-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A large number of compounds are now available that inhibit lun g 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 demon strate that it inhibits NNK-induced lung tumorigenesis by inhibiting t he metabolic activation of NNK. Similar changes appear to occur in hum ans according to data generated in smokers who ate watercress, a sourc e 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. Furthermo re, there is a need to develop suppressing agents for lung cancer that might be applicable in both smokers and ex-smokers.