Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A set of stable nitroxide free radicals that are used as spin labels have been shown to possess metal-independent superoxide dismutase-like activity. Unlike superoxide dismutase (SOD), these compounds are low molecular weight, and readily penetrate into the cell. A representative nitroxide, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (Tempol), was investigated for antimutagenic activity in the XPRT forward mutation assay in CHO AS52 cells. AS52 cells were exposed to hydrogen peroxide, or the hypoxanthine/xanthine oxidase superoxide generating system, in the presence or absence of 10 mM Tempol. Tempol itself was not mutagenic or toxic to AS52 cells. Tempol protected cells nearly completely from the cytotoxic and mutagenic effects of hydrogen peroxide and hypoxanthine/xanthine oxidase. We have previously shown that nitroxides do not alter the extracellular concentration of hydrogen peroxide, and that they are taken up by mammalian cells, suggesting that the antimutagenic activity of Tempol is an intracellular phenomenon.
Environ Mol Mutagen 1992
PMID:Antimutagenicity of a low molecular weight superoxide dismutase mimic against oxidative mutagens. 131 80

The SOS chromotest is a simple short-term genotoxicity assay measuring the induction of gene sfiA in Escherichia coli K-12. The recent availability of SOS tester strains with additional mutations in DNA repair or protection systems allows testing of DNA damaging compounds for genotoxic specificity. E. coli PQ300 differs from the standard SOS tester strain PQ37 in that it contains an additional mutation in gene oxyR that renders it more sensitive to oxidative genotoxins. The generation of reactive oxygen intermediates (ROI) by hydroperoxides (H2O2, t-butyl hydroperoxide, cumene hydroperoxide), gamma-radiation, glucose oxidase, and xanthine oxidase resulted in a more vigorous SOS response in strain PQ300 compared to strain PQ37. PQ300 was also more sensitive than PQ37 for the detection of reducing agents such as ascorbic acid, cysteine, and glutathione, which also alter the redox status of the bacterial cells. However, intercalating agents (adriamycin, bleomycin, and mitomycin C) and the UV- and radiomimetic compound 4-nitroquinoline-1-oxide whose DNA damaging potential are known also to involve ROI did not show significant differences between strains PQ37 and PQ300. It is concluded that the oxyR-deficient strain PQ300 is useful for detecting certain classes of genotoxins that change the oxidative/antioxidative balance of tester bacteria in the SOS chromotest.
Environ Mol Mutagen 1992
PMID:Assessment of oxidative DNA damage in the oxyR-deficient SOS chromotest strain Escherichia coli PQ300. 142 9

Day 9.5 rat embryos were exposed in culture to xanthine/xanthine oxidase generated active oxygen species. Growth and development were assessed after 46 hr of culture. The treatment induced abnormalities of the neural suture, the severity of which increased in a dose-related manner with the concentration of substrate or enzyme. Glutathione (10 mM) or catalase (50 micrograms/ml) either partially or completely abolished the effects of xanthine/xanthine oxidase, whereas the addition of superoxide dismutase (50 micrograms/ml) or desferrioxamine (1mM) did not reduce the number of malformed embryos. These findings suggest that hydrogen peroxide and/or hydroxyl radicals are responsible for the effects of xanthine and xanthine oxidase.
Teratog Carcinog Mutagen 1986
PMID:Malformations induced in cultured rat embryos by enzymically generated active oxygen species. 288 69

The mechanisms by which two quinone-forming compounds, hydroquinone (HQ) and tert-butyl-hydroquinone (tBHQ), induce chromosomal loss and breakage in a prostaglandin H synthase-containing V79 cell line have been investigated using the cytokinesis-block micronucleus assay with CREST antibody staining. Increased frequencies of CREST-positive micronuclei (indicating chromosome loss) and CREST-negative micronuclei (indicating chromosome breakage) were observed following exposure of cells to HQ and tBHQ. The formation of micronuclei by HQ, but not tBHQ, was dependent on arachidonic acid supplementation, indicating activation by prostaglandin H synthase. Since the oxidation of hydroquinones can result in the generation of oxygen radicals, the contribution of oxygen radicals to the formation of chromosomal alterations induced by HQ and tBHQ was investigated. In the presence of a superoxide-generating system consisting of hypoxanthine and xanthine oxidase, a significant increase in micronucleated cells was observed. These induced micronuclei consisted exclusively of CREST-negative micronuclei and their formation was completely inhibited by pretreatment with catalase. Catalase also significantly inhibited the CREST-negative micronuclei induced by HQ and tBHQ. In addition, glutathione treatment inhibited both CREST-positive and negative micronuclei induced by these phenolic compounds. These results indicate that both chromosome loss and breakage are induced by these two quinone-forming agents. Reactive oxygen species contribute to the chromosomal breakage induced by HQ and tBHQ but the observed chromosomal loss appears to result from other mechanisms such as an interference of quinone metabolites with spindle formation.
Environ Mol Mutagen 1994
PMID:Role of oxygen radicals in the chromosomal loss and breakage induced by the quinone-forming compounds, hydroquinone and tert-butylhydroquinone. 785 41

Cells from patients with ataxia-telangiectasia (AT) are more sensitive than cells from normal individuals to a number of compounds which induce DNA damage via oxygen-derived free radical attack. We tested the hypothesis that AT cells would show a sensitivity to reactive oxygen species (ROS) generated by activated inflammatory cells. AT cells were exposed to neutrophils activated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or to xanthine/xanthine oxidase (X/XO), an enzyme system which generates superoxide and hydrogen peroxide. Induced micronuclei (MN) frequencies (corrected for spontaneous MN frequencies) were significantly higher in AT cell cultures than in cultures from normal individuals (comparison of MN frequencies of AT vs. normal cultures: for treatment with activated neutrophils, P = 0.003; for X/XO, P = 0.05). The comet assay was used to determine whether the elevated chromosomal damage in the treated AT cells was due to a difference in strand breakage or its rejoining. X/XO treatment was used in studies of single-stranded (SS) DNA breakage, and X-ray treatment for double-stranded (DS) DNA damage. AT and normal cells showed no significant differences in the initial levels of SS (P = 0.29) or DS (P = 0.91) DNA damage. Likewise, they exhibited similar rejoining kinetics (rejoining half-time for SS = 10 min, for DS = 30 min). These data support the involvement of the AT loci in determining a cell's ability to deal with oxidative stress, although the mechanism underlying this effect has yet to be resolved. The data also suggest that AT patients are at elevated risk of sustaining DNA damage in tissues undergoing inflammatory reactions.
Environ Mol Mutagen 1994
PMID:Response of fibroblast cultures from ataxia-telangiectasia patients to reactive oxygen species generated during inflammatory reactions. 792 23

It has been suggested that reactive oxygen intermediates (ROIs) may have a role in the genotoxic effects of lead (Pb2+) and mercury (Hg2+), but there have not been any definitive studies demonstrating a causal relationship between the induction of ROIs by these metals and mutagenesis. We previously demonstrated, using the transgenic Chinese hamster ovary cell line AS52, that low concentrations (0.1-1 microM) of Pb2+ and Hg2+ are mutagenic. In the present study, using a novel histochemical computer-enhanced image analysis technique, we demonstrate that Pb2+ and Hg2+ induce the formation of H2O2 in AS52 cells by at least two distinct mechanisms. One is characterized by the rapid induction of H2O2 following treatment of cells with concentrations of Pb2+ or Hg2+ below 0.8 and 1 microM, respectively, while the second occurs in AS52 cells treated with concentrations of Pb2+ or Hg2+ greater than 0.8 and 1 microM, respectively. Pb2+ and Hg2+ (0.1-1 microM) had no effect on the activities of partially purified catalase, glutathione peroxidase, or glutathione reductase, important enzymes involved with antioxidant defense, but these metals stimulated the activities of copper-zinc superoxide dismutase (CuZn-SOD) and xanthine oxidase (XO). Allopurinol (50 microM), a specific inhibitor of xanthine oxidase, inhibited the induction of H2O2 by Pb2+ (0.8-1 microM) and Hg2+ (1 microM) and also inhibited Pb2+- and Hg2+-induced mutagenesis. These results demonstrate that Pb2+ and Hg2+ disrupt the redox status of AS52 cells by enhancing the activities of CuZn-SOD and XO. Furthermore, the results of these studies also demonstrate that there is a causal relationship between the induction of H2O2 by these metals and mutagenesis.
Environ Mol Mutagen 1998
PMID:Lead and mercury mutagenesis: role of H2O2, superoxide dismutase, and xanthine oxidase. 965 45

The ability of the ventral prostate cytosolic fractions to biotransform ethanol to acetaldehyde and 1-hydroxyethyl (1HEt) radicals was tested. Acetaldehyde formation was determined by GC-FID analysis in the head space of incubation mixtures. 1HEt was determined by spin trapping with PBN followed by extraction, silylation of the adduct and GC-MS of the product. Prostate cytosol was able to biotransform ethanol to acetaldehyde in the presence of NADH, hypoxanthine, xanthine, caffeine, theobromine, theophylline, and 1,7-dimethylxanthine but not in the presence of N-methylnicotinamide. All these biotransformations were inhibited by allopurinol and were sensitive to heating for 5 min at 100 degrees C. The biotransformation of ethanol to acetaldehyde in the presence of purines as cosubstrates was accompanied by the formation of hydroxyl and 1HEt radicals as detected by GC-MS, and the process was inhibited by allopurinol. Results suggest that prostate cytosolic xanthine oxidase is able to bioactivate ethanol to acetaldehyde and free radicals. The potential of these processes to be involved in tumor-promoting effects of heavy alcohol drinking in conjunction with high meat and/or purines consumption is analyzed. Multifactorial epidemiological studies considering that possibility might be convenient. Teratogenesis Carcinog. Mutagen. 21:109-119, 2001.
Teratog Carcinog Mutagen 2001
PMID:Rat ventral prostate xanthine oxidase bioactivation of ethanol to acetaldehyde and 1-hydroxyethyl free radicals: analysis of its potential role in heavy alcohol drinking tumor-promoting effects. 1122 89

In this study we compared the ability of extractable organic material from particulate and semivolatile fractions of gasoline emission to induce mutations in bacteria and form adducts with calf thymus (CT) DNA with corresponding data obtained from diesel exhaust. Exhaust particles from gasoline-powered passenger cars were collected on filters and semivolatile compounds were collected on polyurethane foam (PUF). The mutagenicity of the soluble organic fraction (SOF) was determined in Salmonella typhimurium strain TA98 and the DNA binding of aromatic compounds in the extracts was assessed by in vitro incubations with CT DNA and rat liver S9 (oxidative activation) or xanthine oxidase (reductive activation) followed by butanol-enhanced (32)P-postlabeling analysis. Semivolatile fractions of gasoline emission collected on PUF formed more CT DNA adducts than filter extracts under all reaction conditions, but showed a lower mutagenic potential than the corresponding particulate samples. This suggests that the capacity of PUF to collect exhaust particle-derived compounds and/or the efficiency of xanthine oxidase and enzymes in the rat liver S9 to activate these compounds to DNA binding metabolites was higher than expected. Gasoline extracts, benzo[a]pyrene and diesel particulate matter (SRM 1650) formed more S9-mediated DNA adducts as their dose increased, although a linear dose-response was not observed for the gasoline exhausts. Lower concentrations of gasoline and diesel extracts bound to DNA with greater efficiency than did 8-fold higher doses, suggesting complex interactions and/or an inhibition of S9 enzyme activities by the high doses. Diesel extracts formed higher levels of adducts than gasoline extracts, especially with the reductive activation system, suggesting that diesel extracts contain high levels of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs). The higher direct-acting Salmonella mutagenicity in diesel extracts in comparison with gasoline extracts is consistent with diesel extracts containing higher concentrations of nitro-PAHs. The results of this study indicate that diesel extracts are more mutagenic and form more DNA adducts than gasoline extracts and that the effects of extract dose on DNA adduct formation are complex.
Environ Mol Mutagen 2003
PMID:Comparison of mutagenicity and calf thymus DNA adducts formed by the particulate and semivolatile fractions of vehicle exhausts. 1287 10

Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defence mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important, therefore, to identify tools for the quantitative analysis of DNA damage in models of neurological disorders. The aim of this study was to compare the susceptibility of DNA to oxidative stress in cells freshly dissociated from the mouse brain, to that in cultured brain cells. Both primary cultures and a continuous cell line of astrocytes were considered. All cells were treated by xanthine/xanthine oxidase, a superoxide generator or hydrogen peroxide, applied alone or in the presence of the oxygen radical scavengers, superoxide dismutase, catalase, or ascorbic acid. DNA damage, quantified with the Comet assay, was consistent in all the different cell preparations exposed to oxidative stress, and was attenuated in similar ways by superoxide dismutase and catalase, scavengers of superoxide anion and hydrogen peroxide, respectively. The results with ascorbic acid were more variable, presumably because this compound may switch from anti- to pro-oxidant status depending on its concentration and other experimental conditions. Overall, similar responses were found in freshly dissociated and cultured brain cells. These results suggest that the Comet assay can be directly applied to cells freshly dissociated from the brain of rodents, including models of neurological disorders, such as stroke models and animals with targeted mutations that mimic human diseases.
Teratog Carcinog Mutagen 2003
PMID:Oxygen-induced DNA damage in freshly isolated brain cells compared with cultured astrocytes in the Comet assay. 1469 79

For centuries, plants have been used in traditional medicines and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the effects of extracts of Acacia salicina leaves on the genotoxicity of benzo[a]pyrene (B(a)P) and nifuroxazide in the SOS Chromotest. Aqueous, total oligomers flavonoids (TOF)-enriched, petroleum ether, chloroform, ethyl acetate, and methanol extracts were prepared from powdered Acacia leaves, and characterized qualitatively for the presence of tannins, flavonoids, and sterols. All the extracts significantly decreased the genotoxicity induced by 1 microg B(a)P (+S9) and 10 microg nifuroxazide (-S9). The TOF-enriched and methanol extracts decreased the SOS response induced by B(a)P to a greater extent, whereas the TOF-enriched and the ethyl acetate extracts exhibited increased activity against the SOS response produced by nifuroxazide. In addition, the aqueous, ethyl acetate, and methanol extracts showed increased activity in scavenging the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) free radical, while 100-300 microg/ml of all the test extracts were active in inhibiting O2-production in a xanthine/xanthine oxidase system. In contrast, only the petroleum ether extract was effective at inhibiting nitroblue tetrazolium reduction by the superoxide radical in a nonenzymatic O2- -generating system. The present study indicates that extracts of A. salicina leaves are a significant source of compounds with antigenotoxic and antioxidant activity (most likely phenolic compounds and sterols), and thus may be useful for chemoprevention.
Environ Mol Mutagen 2007 Jan
PMID:Antigenotoxic activities of crude extracts from Acacia salicina leaves. 1717 9


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