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 w eek, for 5 months to a mixture of cigarette sidestream and mainstream smoke (89%-11%; total suspended particulates 80-150 mg/m(3)), 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 incre ased 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 chemopr eventive agents were evaluated: green tea, phenethyl isothiocyanate (PEITC) , acetylsalicylic acid (ASA), N-acetylcysteine (NAC), p-XSC (1, 4-phenylene -bis-1-[methylene]selenocyanate, ), d-limonene (DL), and a mixture of PEITC and BITC (benzyl isothiocyanate). In animals exposed to tobacco smoke, non e of these agents reduced lung tuner multiplicity or incidence. As a contro l, 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 in jected 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 central v alues. On the other hand, dietary mixture of myoinositol and dexamethasone was not only highly protective against NNK, but reduced lung tumor multipli cities and incidence in smoke-exposed animals to control values. This effec t was also seen when the animals were fed the myo-inositol-dexamethasone mi xture once they were removed fr om smoke. It is concluded that in animal st udies it might be preferable to evaluate the effectiveness of putative chem opreventive agents against full tobacco smoke rather than against selected model compounds. The observations made with myo-inositol-dexamethasone sugg est that people who have recently quit smoking might benefit the most from active chemoprevention.