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Toxicological Sciences 69, 23-29 (2002)
Copyright © 2002 by the Society of Toxicology

CARCINOGENICITY

Lung Tumor Development in Mice Exposed to Tobacco Smoke and Fed ß-Carotene Diets

Ute C. Obermueller-Jevic*,1, Imelda Espiritu{dagger}, Ana M. Corbacho*, Carroll E. Cross* and Hanspeter Witschi{dagger},2

* Center for Comparative Respiratory Biology and Medicine, Department of Medicine, School of Medicine, University of California, Davis, California; and {dagger} Center for Health and the Environment and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616

In human clinical trials it was found that the putative chemopreventive agent ß-carotene not only failed to protect active smokers against the carcinogenic action of tobacco smoke, but actually increased their risk of developing lung cancer. In preclinical animal studies, ß-carotene had been effective against some chemically induced cancers, but not against tumors in the respiratory tract. We exposed male strain A/J mice to tobacco smoke at a concentration of 140 mg/m3 of total suspended particulate matter, 6 h a day, 5 days a week, for either 4 or 5 months, followed by a recovery period in air for 4 or 5 months, or for 9 months without recovery period. ß-carotene was added in the form of gelatin beadlets to the AIN-93G diet either during or following tobacco smoke exposure at concentrations of 0.005, 0.05 and 0.5%. In the supplement-fed animals, plasma and lung levels of ß-carotene were higher than they were in animals fed control diets. Exposure to tobacco smoke increased rather than decreased plasma ß-carotene levels, but had no significant effect on lung levels. After 9 months, lung tumor multiplicities and incidence were determined. Tobacco smoke increased both lung tumor multiplicities and incidences, but ß-carotene failed to modulate tumor development under all exposure conditions. Animal studies in a model of tobacco smoke carcinogenesis would thus have predicted the absence of any beneficial effects of ß-carotene supplementation in current or former smokers, but would have failed to anticipate the increase in lung cancer risk.

Key Words: ß-carotene; lung tumors; cigarette smoke; chemoprevention; strain A mice.


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