88847-89-6Relevant articles and documents
Hydantoin derivative formation from oxidation of 7,8-dihydro-8-oxo- 2′-deoxyguanosine (8-oxodG) and incorporation of 14C-labeled 8-oxodG into the DNA of human breast cancer cells
Sang, Soo Hah,Kim, Hyung M.,Sumbad, Rhoda A.,Henderson, Paul T.
, p. 3627 - 3631 (2005)
One-electron oxidation of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG) yielded a guanidinohydantoin derivative (dGh) and a spiroiminodihydantoin derivative (dSp), both putatively mutagenic products that may be formed in vivo. The nucleoside dGh was the major product at room temperature, regardless of pH. The results are contrary to previously published model studies using 2′,3′,5′-triacetoxy-8-oxo-7,8- dihydroguanosine (Luo, W.; Miller, J. G.; Rachlin, E. M.; Burrows, C. J. Org. Lett. 2000, 2, 613; Luo, W.; Miller, J.G.; Rachlin, E.M.; Burrows, C.J. Chem. Res. Toxicol. 2001, 14, 927), who observed a spiroiminodihydantoin derivative as the major product at neutral pH. Clearly, the functional groups attached to the ribose moiety of 8-oxodG influence the oxidation chemistry of the nucleobase derivative. To explore this chemistry in vivo, 14C-labeled 8-oxodG was synthesized and incubated with growing MCF-7 human breast cancer cells, resulting in the incorporation of the compound into cellular DNA as measured by a novel accelerator mass spectrometry assay.
Susceptibility of channel catfish (Ictalurus punctatus) and brown bullhead (Ameriurus nebulosus) to oxidative stress: a comparative study
Hasspieler, Bruce M.,Behar, Jeffrey V.,Carlson, David B.,Watson, David E.,Giulio, Richard T. Di
, p. 53 - 64 (1994)
Many pollutants in aquatic systems have been shown to exert toxic effects related to oxidative stress. Biochemical parameters of xenobiotic metabolism and oxidative stress were examined in two benthic fish species, channel catfish and brown bullhead, which differ in their apparent susceptibility to pollutant-mediated neoplasia. These parameters included enzyme activities and production of reactive oxygen species by hepatic subcellular fractions. Hepatic ethoxyresorufin O-deethylase (EROD) activity was markedly higher in catfish than in bullhead. This interspecific difference was also observed following induction of EROD activities by β-naphthoflavone (βNF). Conversely, hepatic microsomal cytochrome P-450 reductase (P-450R) activity was higher in bullhead and was unaffected in both species by βNF treatment. Hepatic catalase, DT diaphorase, glutathione reductase, glutathione S-transferase and total glutathione content were significantly higher in catfish as well. Hepatic glutathione peroxidase activity was significantly higher in bullhead. No significant interspecific difference was observed in hepatic superoxide dismutase activity. Cytosolic rates of menadione-mediated superoxide anion and hydrogen peroxide production were higher in pooled catfish liver samples as compared to bullhead. Conversely, microsomal rates of superoxide and hydrogen peroxide production were higher in bullhead, consistent with relative P-450R activities in the two species. Catfish liver homogenate was more effective than bullhead homogenate at inhibiting iron/ascorbate-mediated production of 8-hydroxydeoxyguanosine (8-OHdG) in vitro. - Keywords: Oxidative stress; Channel catfish; Brown bullhead; Menadione; Antioxidant
Measurement of oxidative DNA damage by catechol estrogens and analogues in vitro
Mobley, James A.,Bhat, Abhijit S.,Brueggemeier, Robert W.
, p. 270 - 277 (1999)
The growth-promoting effects of estrogens in hormone-dependent tumor tissues involve receptor-mediated pathways that are well-recognized; however, the role of estrogens in tumor initiation remains controversial. Estrogen metabolites, primarily the catechol estrogens (CE's), have been implicated in tumor initiation via a redox cycling mechanism. We have developed metabolically stable CE analogues for the study of receptor versus redox cycling effects on DNA damage. Comparisons between hydroxy estradiols (HE2's), methoxy estradiols (ME2's), and hydroxymethyl estradiols (HME2) in potentiometric and DNA damaging studies were made. DNA damage was assessed in calf thymus DNA using 8-oxo-2'-deoxyguanosine (8-oxo-dG) as a genotoxic marker for oxidative stress. Increases in the number of 8-oxo-dG/105 dG were significant for each 2-HE2 and 4-HE2. Cu(II)SO4, a transition metal known to catalyze the redox cycling of o-quinones, substantially increased the amount of DNA damage caused by both CE's. However, DNA damage was only observed at concentrations of 10 μM or higher, much greater than what is found under physiologic conditions. Furthermore, the presence of endogenous antioxidants such as glutathione, SOD, and catalase drastically reduced the amount of DNA damage induced by high concentrations of 2-HE2. There was no DNA damage observed for the non-redox cycling HME2's, making these compounds useful probes in the study of receptor-mediated carcinogenesis. Thus, both 2- HE2 and 4-HE2 are capable of producing oxidative DNA damage at micromolar concentrations in vitro. However, since the amount of CE's has not been shown to surpass nanomolar levels in vivo, it is unlikely that free radical production via redox cycling of CE's is a causative factor in human tumorigenesis.
Dietary Antioxidants Fail in Protection against Oxidative Genetic Damage in In Vitro Evaluation
Sun, Mingzhou,Sakakibara, Hiroyuki,Ashida, Hitoshi,Danno, Gen-Ichi,Kanazawa, Kazuki
, p. 2395 - 2401 (2000)
Carcinogenesis is believed to be induced through the oxidative damage of DNA, and antioxidants are expected to suppress it. So, the polyphenolic antioxidants in daily foods were investigated to see whether they protect against genetic damage by active oxygen. In the evaluation, we used a bioassay and a chemical determination, a Salmonella mutagenicity test for mutation by a N-hydroxyl radical from one of the dietary carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and the formation of 8-hydroxyl (8-OHdG) from 2′-deoxyguanosine (2′-dG) in a Fenton OH-radical generating system. Thirty-one antioxidants including flavonoids were compared in terms of radical-trapping activity with bacterial DNA and 2′-dG. Antioxidants inhibited the mutation but the IC50 values were in the mM order. Against 8-OHdG formation, only α-tocopherol had a suppressive effect with an IC50 of 1.5 μM. Thus, except α-tocopherol, the dietary antioxidants did not scavenge the biological radicals faster than bacterial DNA and intact 2′-dG, indicating that they failed to prevent oxidative gene damage and probably carcinogenesis.
Antioxidant Properties of Novel Tetraoxygenated Phenylindan Isomers Formed during Thermal Decomposition of Caffeic Acid
Guillot, Francois L.,Malnoe, Armand,Stadler, Richard H.
, p. 2503 - 2510 (1996)
Mild pyrolysis (228 °C, 15 min) of rosmarinic, chlorogenic, and caffeic acids increased their antioxidative efficacy in a biological rat liver membrane assay by 4-, 11-, and 460-fold, respectively. The active components in the caffeic acid pyrolysates were identified as the recently isolated novel tetraoxygenated 1,3-cis- and 1,3-trans-phenylindan isomers, which showed comparable IC50 values (0.041 and 0.04 μM, respectively) and were ?8-fold more active than butylated hydroxytoluene (BHT). Comparison of nonroasted, light-roasted, and dark-roasted coffee extracts showed that the degree of roasting is positively correlated to the inhibition of lipid peroxidation in rat liver membranes. The potent reducing properties of the phenylindan isomers resulted in (a) prooxidative effects at relatively higher concentrations in an ethyl linoleate peroxidation assay, and (b) promotion of hydroxylation of 2′-deoxyguanosine to afford 8-oxo-2′-deoxyguanosine. However, the results of the rat liver homogenate model system show that pyrolysis of caffeic acid and its esters chlorogenic acid and rosmarinic acid can procure potent antioxidants and underlines the potential use of heat processing to generate novel bioactive molecules.
High-intensity UV laser photolysis of DNA and purine 2'- deoxyribonucleosides: Formation of 8-oxopurine damage and oligonucleotide strand cleavage as revealed by HPLC and Gel electrophoresis studies
Angelov,Spassky,Berger,Cadet
, p. 11373 - 11380 (1997)
Emphasis was placed in this work on the measurement of purine oxidation products generated upon nano- and picosecond UV laser biphotonic photolysis of 2'-deoxyadenosine, 2'-deoxyguanosine, calf thymus DNA, and a synthetic duplex oligonucleotide (37-mer) in aerated aqueous solutions. The overall formation of 8-oxo-7,8-d hydro- 2'-deoxyguanosine and 8-oxo-7,8-dihydro-2' - deoxyadenosme was determined using a HPLC-electrochemical assay. Denaturing gel electrophoresis analysis in association with a formamidopyrimidineNA glycosylase treatment was applied to reveal the sites recognized by this DNA repair enzyme. Both 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8 dihydro-2'-deoxyadenosine were shown to be minor decomposition products of the related nucleoside purine radical cations in agreement with earlier observations. Interestingly, a dramatic increase in the yield of both photoproducts, this applying particularly to 8-oxo-7,8-dihydro-2'- deoxyguanosine, was observe in DNA. It should be noted that the yield of 8- oxo-7,8-dihydro-2'-deoxyguanosine was about 3-fold lower in heat-denatured DNA than in double-stranded DNA. These observations provide strong support to the significant involvement of base stacking and probably DNA solvatation in the chemical reactions of the purine radical cations. Other interesting information dealt with the similarity in the level of 8-oxo-7,8-dihydro-2'- deoxyguanosine and the number of formanidopyrimidine- DNA glycosytase sensitive guanine lesions. This strongly suggests that the latter formidopyrimidine-DNA glycosyiase pine nucleoside is the major DNA photodamaged product recognized by the DNA repair glycosylase. Another striking feature is the almost 10-fold decrease in the saturation dose E(s) for the two-quantum ionization of the guanine base in double-stranded DNA as compared to that observed for free 2'-deoxyguanosine. This can be explained by either an enhancement of the quantum yield of photoionization from the intermediate excited state in DNA (φ2) and/or hole migration with preferential trapping by guanine residues.
Sources of 2,5-diaminoimidazolone lesions in DNA damage initiated by hydroxyl radical attack
Thomas, Caroline Suzanne,Pollard, Hannah Catherine,Razskazovskiy, Yuriy,Roginskaya, Marina
, p. 517 - 524 (2020/09/07)
The present study reports radiation-chemical yields of 2.5-diaminoimidazolone (Iz) derivatives in X-irradiated phosphate-buffered solutions of guanosine and double-stranded DNA. Various gassing conditions (air, N20/O2 (4:1), N2O, vacuum) were employed to elucidate the contribution of several alternative pathways leading to Iz in reactions initiated by hydroxyl radical attack on guanine. In all systems, Iz was identified as the second by abundance guanine degradation product after 8-oxoguanine, formed in 1:5 (guanosine) and 1:3.3 (DNA) ratio to the latter in air-saturated solutions. Experimental data strongly suggest that the addition of molecular oxygen to the neutral guanine radical G(-H)? plays a major in Iz production in oxygenated solutions of double-stranded DNA while in other systems it may compete with recombination of G(-H)? with superoxide and/or alkyl peroxyl radicals. The production of Iz through hydroxyl radical attack on 8-oxoguanine was also shown to take place although the chemical yield of Iz (ca 6%) in this process is too low to compete with the other pathways. The linearity of Iz accumulation with dose also indicates a negligible contribution of this channel to its yield in all systems.
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)
