NO - Besoin d'assistance

Mechanisms and Biomarkers (WG 4) page 44
__________________________________________________________________________________________
Car + ROO . → [OO-Car-OOR] .
The generation of these carotenoid peroxyl radicals could propagate lipid peroxidation within
membranes. This prooxidant effect is dependent upon several factors such as oxygen partial
pressure, concentration of the carotenoid, synergism with other antioxidants.
Partial Pressure of Oxygen - In vitro studies indicate that at low oxygen tensions, carotenoids
behave as a chain breaking antioxidants whilst at higher tensions they exhibits prooxidant
behaviour. This was demonstrated by Hill when β-carotene was reacted with a
trichloroperoxyl radical. At low partial pressures of oxygen only electron transfer occurred to
produce a carotenoid cation radical. When the same reaction was repeated in air and oxygen
saturated solutions a radical cation and a second species [CCl3OO-car] . were detected.
Following the outcome of several recent intervention trials, β-carotene (as a supplement) has
attracted some adverse publicity in its role as a cancer chemopreventive agent. The Alpha
Tocopherol, Beta-Carotene cancer prevention study (ATBC) indicated that male Finnish
smokers who received β- carotene had an 18% increase in the incidence of lung cancer. This
outcome was confirmed during the US Carotene and Retinol Efficiency Trial (CARET) study,
in which a group of smokers receiving the combination of β-carotene and retinol had a 28%
increase in the incidence of lung cancer, compared to the control group. In addition, the large
U.S. Physicians Health Study indicated that there was no overall effect of supplemental β-
carotene on lung or other cancers.
This raises a dilemma in that a substantial body of evidence indicates that dietary carotenoids
are important in reducing the incidence of certain cancers, whilst supplements of an individual
carotenoid demonstrated apparent prooxidant activity increasing cellular damage.
There is an uneven distribution of oxygen partial pressures in the human body, e.g. 100
mmHg at the alveoli in the lung, approximately 40 mmHg in venous blood and as low as 5-15
mmHg in the tissues. However, in vitro studies regarding the antioxidant nature of the
carotenoids are normally performed under atmospheric partial pressures of oxygen, which
would promote the prooxidant nature of the carotenoids (see also chapter 4). Clearly this is
not representative of the in vivo situation. In the light of the CARET study this is of particular
importance, as the increased partial pressure of oxygen at the lung surface would have
potentiated the pro-oxidant effect of the carotenoid in smokers.