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Mechanisms and Biomarkers (WG 4) page 60
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of DNA oxidation considered (Podmore et al., 1998; Cooke et al., 1998; Rehman et al.,
1998). It has been also hypothesized that vitamin C can significantly influence mononuclear
cell DNA, serum, and urinary 8OHdG levels in vivo and that, probably through its redox
properties, may stimulates the repair of 8OHdG in DNA/nucleotide pool. In fact the authors
found an increase of 8OHdG in urine several weeks after the end of vitamin C
supplementation (500 mg/day), while the levels of the oxidized base decreased in DNA
during supplementation and returned to basal level at washout. Thus, the authors suggested
that vitamin C may have some form of residual effect, an apparent pro-oxidant effect.
Another explanation was that vitamin C may not act as an antioxidant per se but may
promote the removal of 8-oxodG from the DNA and/or nucleotide pool upregulating the
repair enzymes (Cooke et al., 1998; Rehman et al., 1998).
Other authors reported that vitamin C supplementation may have prooxidant effect (Podmore
et al., 1998); the interaction of vitamin C with metal ions produce damage but whether this
mechanism occurs in vivo has not been definitively demonstrated (Carr and Frei, 1999b).
Experiments using purified DNA or isolated nuclei (Drouin et al., 1996; Hu et al., 1997)
confirm the pro-oxidant action of vitamin C in the presence of metal ions in vitro. In absence
of metal ions, on the contrary, vitamin C seems to inhibit DNA oxidative damage in vitro
(Fisher-Nielsen et al., 1992; Noorozi et al., 1998; Pflaum et al., 1998) but also some
exception are reported (Singh, 1997; Anderson et al., 1994).
Recently the ingestion of 2 g vitamin C did not cause any adverse effect on chromosome
damage, apoptosis and necrosis in lymphocytes of people with normal Fe levels and absence
of excessive oxidative stress (Crott and Fenech,1999).
By using the comet assay to quantify DNA damage, Anderson et al. (1994) by supplementing
primary lymphocytes ex vivo showed that vitamin C had a protective effect at low doses
(40µmol/L) but an exacerbating effect at high doses (200 µmol/L).
Thus data on vitamin C and DNA damage after in vivo supplementation are still conflicting
and not exaustive to definitely demonstrate the role of vitamin C in antioxidant protection.
Combined supplementation - Just few data are available on the effect of combined
supplementation against DNA damage in humans. The intake of an antioxidant mixture
(vitamin A, C, E, β-carotene, folic acid, rutin) for 4 months by two groups of people (young
and aged donors) decreased lymphocyte micronuclei induced in vitro by gamma-radiation
(Gaziev et al., 1996).
Also Duthie et al. (1996) found a decrease in endogenous lymphocyte DNA damage