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 meek to a mix ture of 89% cigarette sidestream smoke and 11% mainstream smoke. Total susp ended 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 pe riod in air. Lung tumor multiplicity was 2.4 and incidence 89%. Animals exp osed to filtered air had 1.0 tumor per lung (65% incidence). In animals kep t 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 in cidence was 62%. These values were significantly (P < 0.01) lower than in a nimals exposed to smoke and identical to values seen in controls. In animal s fed a diet containing 250 mg/kg each of phenethyl isothiocyanate and benz yl isothiocyanate during the entire 9 months, lung tumor multiplicity was 2 .1 and incidence 96%, not significantly different from animals exposed to s moke and fed control diet. In experiment 2, animals were exposed for 5 mont hs to smoke, followed by a 4 month recovery period in air and were fed duri ng the entire period a diet containing either D-limonene or 1,4-phenylenebi s(methylene)selenoisocyanate (p-XSC). In animals exposed to tobacco smoke a nd fed control diet, lung tumor multiplicity was 2.8, whereas in the animal s fed D-limonene it was 2.6 and in the animals fed p-XSC it was 2.4. The di fferences to the controls were statistically not significant. It was conclu ded that myoinositol-dexamethasone successfully prevents the development of tobacco smoke-induced lung tumors even if administered when the animals ha ve 'quit' smoking, On the other hand, agents otherwise shown to prevent lun g tumor formation following administration of 4-(methylnitrosamino)-l-(3-py ridyl)butanone or benzo[a]pyrene were ineffective against tobacco smoke.