Abstract
Results from some intervention trials indicated that
supplemental b-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 b-carotene and cigarette smoke condensate
(tar) on the formation of lipid peroxidation products in rat
lung microsomal membranes enriched in vitro with
varying b-carotene concentrations (from 1 to 10 nmol/
mg prot) and then incubated with tar (6–25 mg/ml) under
different pO2. As markers of lipid peroxidation, we
evaluated the levels of conjugated dienes and malondialdehyde,
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), b-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. Consistent with this finding, the
addition of a-tocopherol (25 mM) prevented the prooxidant
effects of the carotenoid. b-Carotene auto-oxidation,
measured as formation of 5,6-epoxy-b,b-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.
Lingua originale | English |
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pagine (da-a) | 2383-2391 |
Numero di pagine | 9 |
Rivista | Carcinogenesis |
Stato di pubblicazione | Pubblicato - 2006 |
Keywords
- BETA-CAROTENE
- CIGARETTE SMOKE aqueous extract
- LUNG CANCER