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Mechanisms and Biomarkers (WG 4) page 61
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(oxidised bases) and an increased protection from ex vivo oxidative damage giving subjects
(smokers and nonsmokers) vitamin C, E and β-carotene for up to 40 weeks.
Nutritional status - Several authors tried to demonstrate whether the levels of endogenous
antioxidants are related to DNA damage with conflicting results (Lenton et al., 1999; Collins
et al., 1998; Duthie et al., 1996).
In a cross-sectional analysis of heavy smokers, polycyclic aromatic hydrocarbons (PHA)-
DNA adducts were inversely associated with plasma levels of β-carotene and α-tocopherol
(Mooney et al.,1997). Furthermore the two micronutrients were significantly correlated, and
when β-carotene was low, α-tocopherol had a significant protective effect on adducts but not
when β-carotene was high. The interaction observed suggest that several micronutrients may
act in concert to protect from oxidative damage.
A correlation was also found between plasma ascorbic acid and β-carotene and mutagen
sensitivity assessed by bleomycin induced chromosomal breaks (Kucuk, 1995).
It has been reported that vitamin C and β-carotene are lower in smokers than in non smokers
while no significant difference was found for α-tocopherol levels (Lee et al., 1998). These
results were interpreted suggesting that vitamin C and β-carotene are more vulnerable to
smoking-induced ROS.
Results from a recent study (Bianchini et al., 2000) show that women from Spain had higher
levels of 8-oxo-7,8-dihydro-2’-deoxyguanosine with respect to women fro Sweden. This is in
contrast with the hypothesis generally accepted that a Mediterranean diet rich in α-tocopherol
and carotenoids protects cells against oxidative DNA damage. The authors also suggested
that these results could be attributed to the consumption of foods other than fruit and
vegetables, including fats. Further studies are necessary to evaluate whether mutagen
sensitivity may be affected by plasma levels of certain nutrients and be modified by dietary
intervention.
Immunomodulation
Vitamin C, has been shown, in animal and human studies to be rapidly depleted in several
cancers, infectious diseases, and surgical trauma when oxidative stress was involved. It
appears to be involved at all stages in the immune response. One important site is that of
delayed hypersensitivity which recovers on Vitamin C repletion (Jacobet al, 1991).