Reduction in free-radical-induced DNA strand breaks and base damage through fast chemical repair by flavonoids

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 x 10(7) 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 microM 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.

Reactions of Peroxynitrite with Phenolic and Carbonyl Compounds: Flavonoids are not Scavengers of Peroxynitrite

“…Recently, it has been shown that DNA strand breaks induced by ionizing radiation were rapidly repaired by flavonoids [31]. This observation supports the notion that dietary flavonoids protect by repairing damage, as vitamin C does, rather than by direct scavenging of peroxynitrous acid.…”

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

“…Structurally important features defining the reduction potential of flavonoids are the hydroxylation pattern, a 3 ,4 -dihydroxy catechol structure in the B-ring, the planarity of the molecule and the presence of 2,3-unsaturation in conjugation with a 4-oxo function in the C-ring. Many studies have described the antioxidant efficacy of flavonoids in inhibiting the lipid peroxidation [29,82,171] and other biomolecules such as proteins and DNA [7,20,169] in vitro. Of particular importance to neurodegenerative diseases such as Parkinson's disease is the ability of flavonoids to inhibit peroxynitrite-mediated oxidation of dopamine and peroxynitrite-mediated nitration of tyrosine in vitro by a structure-dependent mechanism involving either the oxidation or nitration of the flavonoid ring system [98,150,151].…”

Measurement of the influence of flavonoids on DNA repair kinetics using the comet assay

“…These data indicate that quercetin treatment may increase non-specific endonuclease activity and that sakuranetin treatment increases both non-specific and specific enzymatic activities. DNA damage (Wasson et al, 2008); (ii) donors of electron or H atom to repair some oxidative DNA damages (Anderson, Amarasinghe, Fisher, Mak, & Packer, 2000); (iii) inducers of apoptosis (Ramos, 2007); (iv) modulators of cellular proliferation (Godlewski, Slazak, Zabielski, Piastowska, & Gralak, 2006); (v) inhibitors of mutagens activation, notably by CYP450 (Hatch, Lightstone, & Colvin, 2000) and activators of phase II detoxification enzymes (Harris & Waring, 2008); (vi) modulators of cell sensibility to chemotherapy (Lambert & Yang, 2003); (vii) angiogenesis inhibitors (Kale et al, 2008); and (viii) suppressors of matrix metalloproteinases secretion and of tumor invasive behavior (Kandaswami et al, 2005). Overall the biological importance and contribution of each mechanism to the protective effect of flavonoids remain unknown and additional mechanisms are still actively investigated.…”