The chemopreventive effects of orally administered dexamethasone in Strain A/J mice following cessation of smoke exposure.
Male Strain A/J mice were exposed for 6 mo, 6 h/d, 5d/wk to a mixture of cigarette sidestream and mainstream smoke with an average total suspended particulate concentration of 156 mg/m3. They then were removed into air and fed diet AIN93M containing 0.5 mg/kg of dexamethasone until killed 4 mo later for the evaluation of lung tumor multiplicities. In animals kept in air, an average of 1.3 tumors per lung was found, and in tobacco-smoke-exposed animals the average number of tumors per lung was 2.2 (p<.05). Addition of dexamethasone to the diet reduced lung tumor multiplicities in the tobacco smoke exposed animals to 1.4 (64% of control values), not quite statistically significant. In animals not exposed to tobacco smoke, however, dexamethasone significantly decreased lung tumor multiplicities to 46% of control values. In animals injected with the tobacco-smoke-specific carcinogen NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone], dietary dexamethasone significantly reduced lung tumor multiplicities to 38% of controls. It is concluded that the dietary intake of dexamethasone against full tobacco smoke might show improved chemopreventive activity when combined with other agents.
Witschi
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Center for Health and the Environment, University of California, Davis, California 95616, USA. hrwitschi@ucdavis.edu
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D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens / Q000008:administration & dosage; D018890:Chemoprevention; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D008175:Lung Neoplasms / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009602:Nitrosamines / Q000008:administration & dosage; D012907:Smoking / Q000009:adverse effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D009602:Nitrosamines; D014028:Tobacco Smoke Pollution; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D003907:Dexamethasone