Carcinogenesis Advance Access published online on May 16, 2006
Carcinogenesis, doi:10.1093/carcin/bgl074
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1 Institute of General Pathology, Catholic University School of Medicine, Rome, Italy
* To whom correspondence should be addressed. Results from some intervention trials indicated that supplemental
Received December 15, 2005
Revised April 26, 2006
Accepted May 5, 2006
CANCER BIOLOGY
Dual role of
P. Palozza 1 *,
S. Serini 1,
S. Trombino 2,
L. Lauriola 3,
F. O. Ranelletti 4,
and
G. Calviello 1
-carotene in combination with cigarette smoke aqueous extract on the formation of mutagenic lipid peroxidation products in lung membranes: dependence on pO2
2 Department of Pharmaceutical Sciences, University of Calabria, Cosenza, Italy
3 Institute of Pathology, Catholic University School of Medicine, Rome, Italy
4 Institute of Histology, Catholic University School of Medicine, Rome, Italy
P. Palozza, E-mail: p.palozza{at}rm.unicatt.it
Abstract 
-carotene enhanced lung cancer incidence and mortality in chronic smokers. The aim of this study was to verify the hypothesis that high concentrations of the carotenoid, under the pO2 present in lung (100-150 mmHg), may exert deleterious effects through a prooxidant mechanism. To test this hypothesis, we examined the interactions of -carotene and cigarette smoke condensate (tar) on the formation of lipid peroxidation products in rat lung microsomal membranes enriched in vitro with varying -carotene concentrations (from 1 to 10 nmoles/mg prot) and then incubated with tar (6-25 µg/ml) under different pO2. As markers of lipid peroxidation, we evaluated the levels of conjugated dienes and malondialdehyde (MDA), possessing mutagenic and pro-carcinogenic activity. The exposure of microsomal membranes to tar induced a dose-dependent enhancement of lipid peroxidation, which progressively increased as a function of pO2. Under a low pO2 (15 mmHg), -carotene acted clearly as an antioxidant, inhibiting tar-induced lipid peroxidation. However, the carotenoid progressively lost its antioxidant efficiency by increasing pO2 (50-100 mmHg) and acted as a prooxidant at pO2 ranging from 100 to 760 mmHg in a dose-dependent manner. Consistently with this finding, the addition of 
-tocopherol (25 µM) prevented the prooxidant effects of the carotenoid. -Carotene autooxidation, measured as formation of 5,6-epoxy-,-carotene, was faster at high than at low pO2 and the carotenoid was more rapidly consumed in the presence of tar. These data point out that the carotenoid may enhance cigarette smoke-induced oxidative stress and exert potential deleterious effects at the pO2 normally present in lung tissue.
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