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.
Witschi
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Institute of Toxicology and Environmental Health and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA 95616, USA. hrwitschi@ucdavis.edu
Uyeminami
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Moran
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D
Espiritu
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I
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D001835:Body Weight; D004032:Diet; D008175:Lung Neoplasms / Q000517:prevention & control*; D008297:Male; D051379:Mice; D012906:Smoke / Q000009:adverse effects*; D016540:Smoking Cessation
D016588:Anticarcinogenic Agents; D012906:Smoke