5614-64-2Relevant academic research and scientific papers
Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents
Kennedy, Laura J.,Moore Jr., Kenneth,Caulfield, Jennifer L.,Tannenbaum, Steven R.,Dedon, Peter C.
, p. 386 - 392 (1997)
Reactive oxygen species, produced endogenously or by exposure to environmental chemicals and ionizing radiation, induce a wide range of DNA lesions. The variety of chemistries associated with different oxidants suggests that each will produce a unique spectrum of DNA damage products. To extend our efforts to relate genotoxin chemistry to DNA damage, we measured both strand breaks and 8-oxoguanine (8-oxoG) in DNA after exposure to γ- radiation, Fe(II)-EDTA/H2O2, Cu(II)/H2O2, and peroxynitrite at concentrations approaching physiological relevance. We found that the ratio of 8-oxoG to strand breaks varied more than 10-fold depending on the oxidizing agent: ~0.4 for Cu(II)/H2O2 and peroxynitrite and ~0.03 for Fe(II)-EDTA/H2O2 and γ-radiation. In the case of Cu(II)/H2O2, the relative proportion of 8-oxoG and strand breaks was found to vary more than 2-fold (0.14-0.37) for different Cu(II) concentrations, consistent with other studies. We were able to detect 8-oxoG formation by peroxynitrite by using low peroxynitrite concentrations in conjunction with a sensitive immunoaffinity/HPLC-ECD methodology. The level of 8-oxoG relative to strand breaks produced by peroxynitrite was higher than that produced by Fe(II)- EDTA/H2O2 and γ-radiation, which is consistent with the altered reactivity or accessibility of a non-hydroxyl radical species produced by peroxynitrite.
Oscillating formation of 8-oxoguanine during DNA oxidation
White, Blanaid,Smyth, Malcolm R.,Stuart, James D.,Rusling, James F.
, p. 6604 - 6605 (2003)
Oxidation of free guanine and guanine in salmon testes ds-DNA by hydroxyl radicals generated with Fenton reagent resulted in oscillating 8-oxoguanine concentrations. These oscillations were superimposed on a general trend of decreasing ratio of [8-oxoguanine]/{[8-oxoguanine] + [guanine]} with time, suggesting that a steady state 8-oxoguanine concentration would not be achieved. Mass spectrometry detected 8-oxoguanine and 5-guanidinohydantoin as products, suggesting that the latter was the product of oxidation of 8-oxoguanine. Guanidinohydantoin and other possible intermediates and products may be involved in a complex mechanism leading to the observed behavior. Oscillatory fluctuations in 8-oxoguanine may need to be considered in assessing its clinical significance as a biomarker for oxidative DNA damage. Copyright
Photooxidative damage of guanine in DG and DNA by the radicals derived from the α cleavage of the electronically excited carbonyl products generated in the thermolysis of alkoxymethyl-substituted dioxetanes and the photolysis of alkoxyacetones
Adam,Arnold,Saha-Moeller
, p. 597 - 604 (2001)
On thermolysis of the methoxy (MeO-TMD), tert-butoxy (tBuO-TMD), and hydroxy (HO-TMD) derivatives of 3,3,4,4-tetramethyl-1,2-dioxetane (TMD) in the presence of dG and calf-thymus DNA, the guanine is oxidized considerably more efficiently than the parent TMD. The same trend in the oxidative reactivity is observed for the photolysis of the corresponding oxy-substituted ketones versus acetone. The oxidative reactivity order in the dioxetane thermolysis, as well as in the ketone photolysis, parallels the ability of the excited ketones to release radicals (determined by spin trapping with DMPO and EPR spectroscopy) upon α cleavage (Norrish-type-I reaction). In the presence of molecular oxygen, the carbon-centered radicals are scavenged to produce peroxyl radicals, which are proposed as the reactive species in the, oxidation of the guanine in dG and calf-thymus DNA.
5-Carboxamido-5-formamido-2-iminohydantoin, in Addition to 8-oxo-7,8-Dihydroguanine, Is the Major Product of the Iron-Fenton or X-ray Radiation-Induced Oxidation of Guanine under Aerobic Reducing Conditions in Nucleoside and DNA Contexts
Alshykhly, Omar R.,Fleming, Aaron M.,Burrows, Cynthia J.
, p. 6996 - 7007 (2015/07/27)
Exogenously and endogenously produced reactive oxygen species attack the base and sugar moieties of DNA showing a preference for reaction at 2′-deoxyguanosine (dG) sites. In the present work, dG was oxidized by HO? via the Fe(II)-Fenton reaction or by X-ray radiolysis of water. The oxidized lesions observed include the 2′-deoxynucleosides of 8-oxo-7,8-dihydroguanine (dOG), spiroiminodihydantoin (dSp), 5-guanidinohydantoin (dGh), oxazolone (dZ), 5-carboxamido-5-formamido-2-iminohydantoin (d2Ih), 5′,8-cyclo-2′-deoxyguanosine (cyclo-dG), and the free base guanine (Gua). Reactions conducted with ascorbate or N-acetylcysteine as a reductant under aerobic conditions identified d2Ih as the major lesion formed. Studies were conducted to identify the role of O2 and the reductant in product formation. From these studies, mechanisms are proposed to support d2Ih as a major oxidation product detected under aerobic conditions in the presence of the reductant. These nucleoside observations were then validated in oxidations of oligodeoxynucleotide and λ-DNA contexts that demonstrated high yields of d2Ih in tandem with dOG, dSp, and dGh. These results identify dG oxidation to d2Ih to occur in high yields leading to a hypothesis that d2Ih could be found from in cells stressed with HO?. Further, the distorted ring structure of d2Ih likely causes this lesion to be highly mutagenic. (Chemical Equation Presented)
HETEROCYCLIC GTP CYCLOHYDROLASE 1 INHIBITORS FOR THE TREATMENT OF PAIN
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Page/Page column 68, (2011/04/19)
The present invention relates to the field of small molecule heterocyclic inhibitors of GTP cyclohydrolase (GCH-I), or a tautomer, prodrug, or pharmaceutically acceptable salt thereof. The invention also features pharmaceutical compositions of the compounds and the medical use of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, or neuropathic pain).
Fe(II) phthalocyanine catalyzed oxidation of dGMP by molecular oxygen
Kuznetsova, Aleksandra A.,Solovyeva, Lyudmila I.,Kaliya, Oleg L.,Lukyanets, Evgeniy A.,Knorre, Dmitri G.,Fedorova, Olga S.
experimental part, p. 4335 - 4338 (2010/04/24)
We show that iron(II)-phthalocyanines are able to catalyze guanosine oxidation by molecular oxygen in the presence of reducing agents such as ascorbic acid and 2-mercaptoethanol. The products of 5′-monophosphate-2′-deoxyguanosine (dGMP) oxidation were dir
Photooxidation of substituted purines in presence of peroxydisulphate in aqueous solution
Swaraga, Midudhula Sudha,Adinarayana, Mundra
, p. 2096 - 2100 (2007/10/03)
Photooxidation of purine bases, viz., caffeine, theobromine, theophylline, xanthine, hypoxanthine, adenine and guanine in aqueous solution has been carried out in presence of peroxydisulphate (PDS). Peroxydisulphate is activated to SO4.- at 254 nm. The reactions are followed by measuring the absorbance of purine bases at their respective γmax]. The rates of reactions are calculated under different experimental conditions. The light intensity is measured using peroxydisulphate solution as standard chemical actinometer. Using reaction rate and light intensity at 254 nm, the quantum yields are calculated. The rates of photooxidation of purine bases are found to increase with increase in [PDS] and independent of [purine]. The increase of light intensity has been found to increase the rate of oxidation. The quantum yields are found to depend on [purine] but independent of [PDS] and light intensity. On the basis of experimental results a probable mechanism is suggested in which peroxydisulphate on photolysis gives sulphate radical anion which initiates the reaction by capturing an electron from C8 position of purine to form purine radical cation. This radical cation deprotonates and undergoes further oxidation to give C(8) hydroxy purine.
Regulation of one-electron oxidation rate of guanine and hole transfer rate in DNA through hydrogen bonding
Kawai, Kiyohiko,Takada, Tadao,Tojo, Sachiko,Majima, Tetsuro
, p. 8083 - 8085 (2007/10/03)
The effects of methyl and bromo groups at C5 of C on the one-electron oxidation rate of G, and on the hole transfer rate in DNA have been investigated. The rates of one-electron oxidation of G and hole transfer from Py·+ to 8-oxo-7,8-dihydrogua
Base modification and strand breakage in isolated calf thymus DNA and in DNA from human skin epidermal keratinocytes exposed to peroxynitrite or 3- morpholinosydnonimine
Spencer, Jeremy P. E.,Wong, Jon,Jenner, Andrew,Aruoma, Okezie I.,Cross, Caroll E.,Halliwell, Barry
, p. 1152 - 1158 (2007/10/03)
Exposure of isolated calf thymus DNA and human skin epidermal keratinocytes to peroxynitrite or the peroxynitrite generator, 3- morpholinosydnonimine (SIN-1), led to extensive DNA base modification. Large increases in xanthine and hypoxanthine, possible deamination products of guanine and adenine, respectively, and in 8-nitroguanine were observed, but only small changes in some oxidized base products were seen. This pattern of damage suggests that hydroxyl radicals were not major contributors to base modification caused by peroxynitrite, as OH· is known to cause multiple oxidative modifications to all four DNA bases. Instead, it seems that reactive nitrogen species play a much greater role in the mechanism of base damage, producing both nitration and deamination of purine bases when DNA or whole cells are exposed to peroxynitrite. If this pattern of damage is unique to peroxynitrite, it might act as a marker of cellular damage by this species in vivo.
N-Hydroxypyridinthione als photochemische Hydroxylradikalquellen zur oxidativen DNA-Schaedigung
Adam, Waldemar,Ballmaier, Daniel,Epe, Bernd,Grimm, Guenther N.,Saha-Moeller, Chantu R.
, p. 2326 - 2328 (2007/10/03)
Keywords: DNA-Oxidationen; Hydroxylradikal; N-Hydroxypyridinthione
