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Reduction in free-radical-induced DNA strand breaks and base damage through fast chemical repair by flavonoids
Authors:Robert F Anderson  Chanchala Amarasinghe  Louisa J Fisher  Wai B Mak  John E Packer
Institution:1. Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland 1, New Zealandr.anderson@auckland.ac.nz;3. Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland 1, New Zealand
Abstract:This paper provides evidence that dietary flavonoids can repair a range of oxidative radical damages on DNA, and thus give protection against radical-induced strand breaks and base alterations. We have irradiated dilute aqueous solutions of plasmid DNA in the absence and presence of flavonoids (F) in a “constant ·OH radical scavenging environment”, k of 1.5 × 107 s-1 by decreasing the concentration of TRIS buffer in relation to the concentration of added flavonoids. We have shown that the flavonoids can reduce the incidence of single-strand breaks in double-stranded DNA as well as residual base damage (assayed as additional single-strand breaks upon post-irradiation incubation with endonucleases) with dose modification factors of up to 2.0 ± 0.2 at F] < 100 μM by a mechanism other than through direct scavenging of ·OH radicals. Pulse radiolysis measurements support the mechanism of electron transfer or H· atom transfer from the flavonoids to free radical sites on DNA which result in the fast chemical repair of some of the oxidative damage on DNA resulting from ·OH radical attack. These in vitro assays point to a possible additional role for antioxidants in reducing DNA damage.
Keywords:Flavonoids  antioxidants  electron transfer  DNA strand breaks  base damage  pulse radiolysis
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