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 language | English (US) |
|---|---|
| Pages (from-to) | 23-29 |
| Number of pages | 7 |
| Journal | Toxicological Sciences |
| Volume | 69 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 2002 |
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Keywords
- β-carotene
- Chemoprevention
- Cigarette smoke
- Lung tumors
- Strain A mice
ASJC Scopus subject areas
- Toxicology
Cite this
Lung tumor development in mice exposed to tobacco smoke and fed β-carotene diets. / Obermueller-Jevic, Ute C.; Espiritu, Imelda; Corbacho, Ana M.; Cross, Carroll E; Witschi, Hanspeter.
In: Toxicological Sciences, Vol. 69, No. 1, 09.2002, p. 23-29.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lung tumor development in mice exposed to tobacco smoke and fed β-carotene diets
AU - Obermueller-Jevic, Ute C.
AU - Espiritu, Imelda
AU - Corbacho, Ana M.
AU - Cross, Carroll E
AU - Witschi, Hanspeter
PY - 2002/9
Y1 - 2002/9
N2 - 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.
AB - 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.
KW - β-carotene
KW - Chemoprevention
KW - Cigarette smoke
KW - Lung tumors
KW - Strain A mice
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UR - http://www.scopus.com/inward/citedby.url?scp=0036738720&partnerID=8YFLogxK
U2 - 10.1093/toxsci/69.1.23
DO - 10.1093/toxsci/69.1.23
M3 - Article
VL - 69
SP - 23
EP - 29
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 1
ER -