Chemoprevention of tobacco-smoke lung carcinogenesis in mice after cessation of smoke exposure.

Male strain A/J mice were exposed for 6 h per day, 5 days per week to a mixture of 89% cigarette sidestream smoke and 11% mainstream smoke. Total suspended particulate concentrations were 137 mg/m(3). In experiment 1, animals were exposed for 5 months to tobacco smoke and given a 4 month recovery period in air. Lung tumor multiplicity was 2.4 and incidence 89%. Animals exposed to filtered air had 1.0 tumor per lung (65% incidence). In animals kept for 5 months in smoke, removed into air and then fed a diet containing a mixture of myoinositol and dexamethasone, tumor multiplicity was 1.0 and incidence was 62%. These values were significantly (P < 0.01) lower than in animals exposed to smoke and identical to values seen in controls. In animals fed a diet containing 250 mg/kg each of phenethyl isothiocyanate and benzyl isothiocyanate during the entire 9 months, lung tumor multiplicity was 2.1 and incidence 96%, not significantly different from animals exposed to smoke and fed control diet. In experiment 2, animals were exposed for 5 months to smoke, followed by a 4 month recovery period in air and were fed during the entire period a diet containing either D-limonene or 1, 4-phenylenebis(methylene)selenoisocyanate (p-XSC). In animals exposed to tobacco smoke and fed control diet, lung tumor multiplicity was 2.8, whereas in the animals fed D-limonene it was 2. 6 and in the animals fed p-XSC it was 2.4. The differences to the controls were statistically not significant. It was concluded that myoinositol-dexamethasone successfully prevents the development of tobacco smoke-induced lung tumors even if administered when the animals have 'quit' smoking. On the other hand, agents otherwise shown to prevent lung tumor formation following administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone or benzo[a]pyrene were ineffective against tobacco smoke.

Chemoprevention of tobacco smoke-induced lung tumors in A/J strain mice with dietary myo-inositol and dexamethasone.

Male A/J strain mice were fed AIN-76A diet supplemented with myo-inositol/dexamethasone (10 g and 0.5 mg/kg diet) or acetylsalicylic acid (300 mg/kg) and exposed for 5 months to a mixture of sidestream and mainstream cigarette smoke at a concentration of 132 mg total suspended particulates/m3. After tobacco smoke exposure, they were allowed to recover for another 4 months in filtered air. In the animals fed AIN-75A diet alone or acetylsalicylic acid, the average number of tumors/lung was 2.1, whereas in the animals given the myo-inositol/dexamethasone diet, the average lung tumor multiplicity was 1.0 (P < 0.05). In animals exposed to filtered air, lung tumor multiplicities were 0.6 for animals fed AIN-76A or myo-inositol/dexamethasone and 1.2 for animals fed acetylsalicylic acid. It was concluded that the combination of myo-inositol and dexamethasone constitutes an effective chemopreventive regimen against tobacco smoke-induced lung tumorigenesis.