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

Ute C. Obermueller-Jevic, Imelda Espiritu, Ana M. Corbacho, Carroll E Cross, Hanspeter Witschi

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24 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)23-29
Number of pages7
JournalToxicological Sciences
Volume69
Issue number1
DOIs
StatePublished - Sep 2002

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Keywords

  • β-carotene
  • Chemoprevention
  • Cigarette smoke
  • Lung tumors
  • Strain A mice

ASJC Scopus subject areas

  • Toxicology

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