Lung tumor development in mice exposed to tobacco smoke and fed beta-carotene diets.

Abstract

In human clinical trials it was found that the putative chemopreventive agent beta-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, beta-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/m(3) 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. beta-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 beta-carotene were higher than they were in animals fed control diets. Exposure to tobacco smoke increased rather than decreased plasma beta-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 beta-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 beta-carotene supplementation in current or former smokers, but would have failed to anticipate the increase in lung cancer risk.

• Authors: Ute C Obermueller-Jevic, Imelda Espiritu, Ana M Corbacho, Carroll E Cross, Hanspeter Witschi
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 69 Issue 1 Pg. 23-9 (Sep 2002) ISSN: 1096-6080 [Print] United States
• PMID: 12215657 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antioxidants
• Smoke
• beta Carotene

Topics

• Animals
• Antioxidants (pharmacology)
• Atmosphere Exposure Chambers
• Chromatography, High Pressure Liquid
• Diet
• Lung Neoplasms (chemically induced, pathology)
• Male
• Mice
• Mice, Inbred A
• Smoke (adverse effects)
• Tobacco (adverse effects)
• beta Carotene (blood, pharmacology)