A reevaluation of the ambident reactivity of the guanine moiety towards hydroxyl radicals.
ABSTRACT Radically different: Contrary to previous proposals, the main reaction of the HO(*) radical with guanosine or 2'-deoxyguanosine is the hydrogen abstraction from the NH(2) moiety to give a guanyl radical. This radical, characterized by a broad band in the visible region (around 610 nm), undergoes tautomerization to the most stable isomer.
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ABSTRACT: Polyhalogenated quinones are a class of carcinogenic intermediates. We found recently that the highly reactive and biologically/environmentally important ·OH can be produced by polyhalogenated quinones and H(2)O(2) independent of transition metal ions. However, it is not clear whether this unusual metal-independent ·OH producing system can induce potent oxidative DNA damage. Here we show that TCBQ and H(2)O(2) can induce oxidative damage to both dG and dsDNA; but surprisingly, it was more efficient to induce oxidative damage in dsDNA than in dG. We found that this is probably due to its strong intercalating ability to dsDNA through competitive intercalation assays. The intercalation of TCBQ in dsDNA may lead to ·OH generation more adjacent to DNA. This is the first report that polyhalogenated quinoid carcinogens and H(2)O(2) can induce potent DNA damage via a metal-independent and intercalation-enhanced oxidation mechanism, which may partly explain their potential genotoxicity, mutagenesis, and carcinogenicity.Scientific Reports 02/2013; 3:1269. · 2.93 Impact Factor
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ABSTRACT: The mitochondrial DNA (mtDNA) encodes for only 13 polypeptides, components of 4 of the 5 oxidative phosphorylation complexes. But despite this apparently small numeric contribution, all 13 subunits are essential for the proper functioning of the oxidative phosphorylation circuit. Thus, accumulation of lesions, mutations and deletions/insertions in the mtDNA could have severe functional consequences, including mitochondrial diseases, aging and age-related diseases. The DNA is a chemically unstable molecule, which can be easily oxidized, alkylated, deaminated and suffer other types of chemical modifications, throughout evolution the organisms that survived were those who developed efficient DNA repair processes. In the last two decades, it has become clear that mitochondria have DNA repair pathways, which operate, at least for some types of lesions, as efficiently as the nuclear DNA repair pathways. The mtDNA is localized in a particularly oxidizing environment, making it prone to accumulate oxidatively generated DNA modifications (ODMs). In this article, we: i) review the major types of ODMs formed in mtDNA and the known repair pathways that remove them; ii) discuss the possible involvement of other repair pathways, just recently characterized in mitochondria, in the repair of these modifications; and iii) address the role of DNA repair in mitochondrial function and a possible cross-talk with other pathways that may potentially participate in mitochondrial genomic stability, such as mitochondrial dynamics and nuclear-mitochondrial signaling. Oxidative stress and ODMs have been increasingly implicated in disease and aging, and thus we discuss how variations in DNA repair efficiency may contribute to the etiology of such conditions or even modulate their clinical outcomes.Mitochondrion 04/2014; · 4.03 Impact Factor
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ABSTRACT: Hydroxyl radical ((•)OH) and one-electron oxidants that may be endogenously formed through oxidative metabolism, phagocytosis, inflammation and pathological conditions constitute the main sources of oxidatively generated damage to cellular DNA. It is worth mentioning that exposure of cells to exogenous physical agents (UV light, high intensity UV laser, ionizing radiation) and chemicals may also induce oxidatively generated damage to DNA. Emphasis is placed in this short review article on the mechanistic aspects of (•)OH and one-electron oxidant-mediated formation of single and more complex damage (tandem lesions, intra- and interstrand cross-links, DNA-protein cross-links) in cellular DNA arising from one radical hit. This concerns DNA modifications that have been accurately measured using suitable analytical methods such as high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Evidence is provided that (•)OH and one-electron oxidants after generating neutral radicals and base radical cations respectively may partly induce common degradation pathways. In addition, selective oxidative reactions giving rise to specific degradation products of (•)OH and one-electron oxidation reactions that can be used as representative biomarkers of these oxidants have been identified.Archives of Biochemistry and Biophysics 05/2014; · 3.37 Impact Factor