Lung tumor development in mice exposed to tobacco smoke and fed beta-carotene diets.
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.
Obermueller-Jevic
Ute C
UC
Center for Comparative Respiratory Biology and Medicine, Department of Medicine, School of Medicine, University of California, Davis, California 95616, USA. ute.obermueller-jevic@basf-ag.de
Espiritu
Imelda
I
Corbacho
Ana M
AM
Cross
Carroll E
CE
Witschi
Hanspeter
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001273:Atmosphere Exposure Chambers; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D012906:Smoke / Q000009:adverse effects*; D019207:beta Carotene / Q000097:blood / Q000494:pharmacology*
D000975:Antioxidants; D012906:Smoke; D019207:beta Carotene