88847-89-6Relevant academic research and scientific papers
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.
Time and concentration dependence of fenton-induced oxidation of dG
Grey, Carl,Adlercreutz, Patrick
, p. 259 - 278 (2006)
The influence of incubation time and Fenton reagent concentrations was investigated on the oxidation of 2′-deoxyguanosine. The compounds identified and quantified, through use of an LC-MS/MS system, were 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8,5′-cyclo- 2′-deoxyguanosine (8,5′cyclodG) and the secondary oxidation products guanidinohydantoin and dehydro-guanidinohydantoin. 8-oxodG and 8,5′cyclodG formed very quickly, reaching a maximum rapidly, but with 8-oxodG a rapid decline occurred thereafter due to its further oxidation into the secondary products, which formed more slowly. Due to the better stability, 8,5′cyclodG correlated better with the general level of oxidation than 8-oxodG. The results emphasize the advantages of measuring other oxidation adducts than 8-oxodG alone. Copyright Taylor & Francis Group, LLC.
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
Hydroxylation of Deoxyguanosine at the C-8 Position in the Thiosulfate-Hydrogen Peroxide Reaction System. Evidence of Hydroxyl Radical Generation in the System
Seto, Hiroshi,Koike, Hiroshi,Sasano, Hideo
, p. 993 - 996 (1994)
The thiosulfate-hydrogen peroxide reaction system generates thiosulfate radical anion and hydroxyl radical.When 2'-deoxyguanosine (dG) was included in the system, it was hydroxylated at the C-8 position, and the hydroxylation was markedly enhanced by addition of a trace amount of iron ion.
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.
Optimization of the workup procedure for the analysis of 8-oxo-7,8-dihydro-2′-deoxyguanosine with electrochemical detection
Hofer, Tim,Moeller, Lennart
, p. 426 - 432 (2002)
The artifactual generation of the biomarker for oxidative stress, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), during the workup procedure for its analysis is a difficult problem to solve, and the responsible factors are unclear. Here, peroxide removal and other antioxidant procedures during workup were compared using a limited amount of rat liver (50 mg) as starting material, with subsequent hydrolysis of 50 μg of DNA. A cold (0 °C) high salt GTC (4 M guanidine thiocyanate) nonphenol DNA extraction method was developed where DNA is quickly isolated. GSH (reduced glutathione) generated artifactual formation of 8-oxodG during the workup procedure, whereas H2O2 removal using catalase, Fe3+ removal and passivation using desferal, peroxide removal using glutathione peroxidase, ebselen and a peroxidase mimic lowered the 8-oxodG levels, all identifying peroxides as the responsible oxidants. Desferal was more protective when excluding Mg2+ and Ca2+ from buffers but was found to disturb the electrochemical detector when repeatedly injected five to six times, even at 100 μM. Addition of the OH-scavenger ethanol in all steps at 2% v/v had no protective effect. Zn2+ was found necessary for efficient DNA hydrolysis using nuclease P1, which was poor below 37 °C. Use of water substitutes was tested but inhibited DNA hydrolysis completely. H218O could, however, work for mass spectrometry methods. Long-term (38 days) storage of 0.5% v/v Triton X-100 generated more 8-oxodG than Tween 20 when incubated with free dG. The cold GTC DNA extraction method was used for analysis of freshly isolated human lymphocytes/monocytes from 60 healthy men using catalase and TEMPO as antioxidants, giving a background level of 0.074 ± 0.027 8-oxodG/105 dG (or 16 8-oxodG/108 nucleotides or 1943 8-oxodG/nuclei) which is probably the lowest value obtained yet. No increase with age was seen. Oxidation of dG to 8-oxodG during workup was found to fit a mathematically defined curve, and a calculated background level of 0.047 8-oxodG/105 dG was obtained. To obtain more reliable results it is recommended that control samples are included during the workup procedure, having an equal amount of cells (or DNA) as the exposed samples.
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.
8-Hydroxy-2′-deoxyguanosine formation and DNA damage induced by a dinuclear manganese(IV) complex and hydrogen peroxide
Kobayashi, Teruyuki,Tsuchiya, Kazuyoshi,Nishida, Yuzo
, p. 2391 - 2392 (1996)
The dinuclear manganese(IV) complex [Mn2O3L2][PF6]2 exhibits high activity for 8-hydroxy-2′-deoxyguanosine formation and relaxation of pBR322 form I DNA in the presence of H2O2, where L = 1,4,7-trimethyl-1,4,7-triazacyclononane; the active species is postulated to be a unidentate peroxide adduct of the manganese(IV) complex.
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.
Spiroiminodihydantoin nucleoside formation from 2′-deoxyguanosine oxidation by [18O-labeled] singlet molecular oxygen in aqueous solution
Martinez, Glaucia Regina,Ravanat, Jean-Luc,Cadet, Jean,De Medeiros, Marisa Helena Gennari,Di Mascio, Paolo
, p. 1326 - 1332 (2007)
The main singlet molecular oxygen (1O2) oxidation products of free 2′-deoxyguanosine (dGuo) in aqueous solution were identified as a pair of diastereomeric spiroiminodihydantoin 2′-deoxyribonucleosides (dSp) together with 8-oxo-7,8-dihydro-2′- deoxyguanosine (8-oxodGuo). In the present work, evidence is provided from 18[1O2] and H218O labeling experiments, using HPLC-ESI-MS/MS, that the formation of dSp is explained by the addition of water to a reactive quinonoid intermediate, and a second reaction pathway leading to dSp involves 1O2 oxidation of initially generated 8-oxodGuo. Copyright
