The Chemopreventive Effects of Orally Administered Dexamethasone in Strain A/J Mice Following Cessation of Smoke Exposure

Abstract

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.

Notes

The authors thank Shanie MacCarty and Loreli Coleman for their competent help with animal care. Research described in this article was supported by Philip Morris USA Inc. and Phillip Morris International.