Successful and not so successful chemoprevention of tobacco smoke-induced lung tumors.

Strain A/J mice underwent whole body exposure for 6 hours a day, 5 days a week, for 5 months to a mixture of cigarette sidestream and mainstream smoke (89%-11%; total suspended particulates 80-150 mg/m3), then were kept for another 4 months in air before being killed for scoring of lung tumors. In 7 independent experiments, lung tumor multiplicity was significantly increased in all 7 trials and lung tumor incidence in 5. When animals were kept for 9 months in smoke, lung tumor multiplicity was not significantly higher than in controls, although lung tumor incidence was. The following chemopreventive agents were evaluated: green tea, phenethyl isothiocyanate (PEITC), acetylsalicylic acid (ASA), N-acetylcysteine (NAC), p-XSC (1,4-phenylenebis[methylene]selenocyanate), d-limonene (DL), and a mixture of PEITC and BITC (benzyl isothiocyanate). In animals exposed to tobacco smoke, none of these agents reduced lung tumor multiplicity or incidence. As a control, the effects of the same agents were examined in A/J mice initiated with 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK) or urethane. In mice injected with NNK, green tea and ASA did not reduce lung tumor multiplicities and NAC had no effect on urethane-induced lung tumors, whereas PEITC, p-XSC and DL reduced NNK-induced tumor multiplicities to 20% to 50% of control values. On the other hand, dietary mixture of myoinositol and dexamethasone was not only highly protective against NNK, but reduced lung tumor multiplicities and incidence in smoke-exposed animals to control values. This effect was also seen when the animals were fed the myo-inositol-dexamethasone mixture once they were removed from smoke. It is concluded that in animal studies it might be preferable to evaluate the effectiveness of putative chemopreventive agents against full tobacco smoke rather than against selected model compounds. The observations made with myo-inositol-dexamethasone suggest that people who have recently quit smoking might benefit the most from active chemoprevention.