Assay of excised oxidative DNA lesions: isolation of 8-oxoguanine and its nucleoside derivatives from biological fluids with a monoclonal antibody column.

Park, Eun M I; Shigenaga, Mark K.; Degan, Paolo; Korn, Tommy S.; Kitzler, Jeffrey W.; Wehr, Carol M.; Kolachana, Prema; Ames, B. N.

doi:10.1073/pnas.89.8.3375

Cited by 277 publications

(155 citation statements)

References 25 publications

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“…8-hydroxy-2-deoxyguanosine is a well accepted marker of oxidative damage to DNA (Park et al, 1992;Mecocci et al, 1993), while 3-nitrotyrosine is produced by peroxynitritemediated tyrosine nitration . 3-NP (10 mg/kg) was administered every 12 hr.…”

Section: Resultsmentioning

confidence: 99%

“…The antisera used include those against 3-nitrotyrosine (monoclonal clone lA6), courtesy of Dr. Joseph Beckman, used at a dilution of 1: 100 for free floating sections ; and 8-hydroxy-2-deoxyguanosine, courtesy of Dr. Bruce Ames, used at a dilution of 1:750 (Park et al, 1992). Preabsorption of antibodies with 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine respectively abolished staining.…”

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confidence: 99%

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Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

et al. 1995

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Nitric oxide may be a key mediator of excitotoxic neuronal injury in the central nervous system. We examined the effects of the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) on excitotoxic striatal lesions. 7-NI significantly attenuated lesions produced by intrastriatal injections of NMDA, but not kainic acid or alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) 7-NI attenuated secondary striatal excitotoxic lesions produced by the succinate dehydrogenase inhibitor malonate, and the protection was reversed by L- arginine but not by D-arginine, 7-NI produced nearly complete protection against striatal lesions produced by systemic administration of 3-nitropropionic acid (3-NP), another succinate dehydrogenase inhibitor, 7-NI protected against malonate induced decreases in ATP, and increases in lactate, as assessed by 1H magnetic resonance spectroscopy. 7-NI had no effects on spontaneous electrophysiologic activity in the striatum in vivo, suggesting that its effects were not mediated by an interaction with excitatory amino acid receptors. 7-NI attenuated increases in hydroxyl radical, 8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine generation in vivo, which may be a consequence of peroxynitrite formation. The present results implicate neuronal nitric oxide generation in the pathogenesis of both direct and secondary excitotoxic neuronal injury in vivo. As such they suggest that neuronal nitric oxide synthase inhibitors may be useful in the treatment of neurologic diseases in which excitotoxic mechanisms play a role.

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Section: Resultsmentioning

confidence: 99%

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Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

et al. 1995

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“…The great genetic variability of the human species makes it likely that the optimal RDA for particular micronutrients will be higher than average for many people. Techniques for noninvasive measurement of DNA damage in humans are clearly relevant (148,149).…”

Section: Progression and Clonal Instabilitymentioning

confidence: 99%

DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis.

Ames

Shigenaga

Gold

1993

Environ Health Perspect

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268

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DNA lesions that escape repair have a certain probability of giving rise to mutations when the cell divides. Endogenous DNA damage is high: 106 oxidative lesions are present per rat cell. An exogenous mutagen produces an increment in lesions over the background rate of endogenous lesions. The effectiveness of a particular lesion depends on whether it is excised by a DNA repair system and the probability that it gives rise to a mutation when the cell divides. When the cell divides, an unrepaired DNA lesion has a certain probability of giving rise to a mutation. Thus, an important factor in the mutagenic effect of an exogenous agent whether it is genotoxic or non-genotoxic, is the increment it causes over the background cell division rate (mitogenesis) in cells that appear to matter most in cancer, the stem cells, which are not on their way to being discarded. Increasing their cell division rate increases mutation and therefore cancer. There is little cancer from nondividing cells. Endogenous cell division rates can be influenced by hormone levels, decreased by calorie restriction, or increased by high doses of chemicals. If both the rate of DNA lesions and cell division are increased, then there will be a multiplicative effect on mutagenesis (and carcinogenesis), for example, by high doses of a mutagen that also increases mitogenesis through cell killing. The defense system against reactive electrophilic mutagens, such as the glutathione transferases, are also almost all inducible and buffer cells against increments in active forms of chemicals that can cause DNA lesions. A variety of DNA repair defense systems, almost all inducible, buffer the cell against any increment in DNA lesions. Therefore, the effect of a particular chemical insult depends on the level of each defense, which in turn depends on the past history of exposure. Exogenous agents can influence the induction and effectiveness of these defenses. Defenses can be partially disabled by lack of particular micronutrients in the diet (e.g., antioxidants). Four endogenous processes leading to significant DNA damage are oxidation (1-3), methylation, deamination, and depurination (2). The importance of these processes is supported by the existence of specific DNA repair glycosylases for oxidative, methylated, and deaminated adducts and a repair system for apurinic sites that are produced by spontaneous depurination (3). Endogenous DNA Damage and MutagenesisDNA damage produced by oxidation appears to be the most significant endogenous damage (4). We estimate that the DNA hits per cell per day from endogenous oxidants are normally 105 in the rat and 104 in the human (5-7). These oxidative lesions are effectively but not perfectly repaired; the normal steady-state level of oxidative DNA lesions is about 106 per cell in the young rat and about twice this in the old rat (6,8). Oxidants are produced as byproducts of mitochondrial electron transport, various oxygen-utilizing enzyme system, peroxisomes, and other processes associated with normal aerobic metabolism...

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“…There are a spectra of DNA lesions generated by ROS, with the most abundant being a base modification to 7,8-dihydro-8-oxoguanine (8-oxoG) (5,6). In vivo measurements estimate a high number (10 5 ) of such oxidatively modified lesions formed in a cell each day (7). Conversion of guanine to 8-oxoG causes a selective mis-incorporation of adenine opposite to 8-oxoG that can lead to G-T transversions in the DNA (8,9).…”

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Hydrogen Peroxide Induces Topoisomerase I-mediated DNA Damage and Cell Death

Daroui

Desai

Li³

et al. 2004

Journal of Biological Chemistry

126

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Reactive oxygen species modify DNA, generating various DNA lesions including modified bases such as 8-oxoguanine (8-oxoG). These base-modified DNA lesions have been shown to trap DNA topoisomerase I (TOP1) into covalent cleavage complexes. In this study, we have investigated the role of TOP1 in hydrogen peroxide toxicity. We showed that ectopic expression of TOP1 in Saccharomyces cerevisiae conferred sensitivity to hydrogen peroxide, and this sensitivity was dependent on RAD9 checkpoint function. Moreover, in the mammalian cell culture system, hydrogen peroxide-induced growth inhibition and apoptosis were shown to be partly TOP1-dependent as evidenced by a specific increase in resistance to hydrogen peroxide in TOP1-deficient P388/ CPT45 murine leukemia cells as compared with their TOP1-proficient parental cell line P388. In addition, hydrogen peroxide was shown to induce TOP1-DNA crosslinks. These results support a model in which hydrogen peroxide promotes the trapping of TOP1 on oxidative DNA lesions to form TOP1-DNA cleavage complexes that contribute to hydrogen peroxide toxicity.

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Assay of excised oxidative DNA lesions: isolation of 8-oxoguanine and its nucleoside derivatives from biological fluids with a monoclonal antibody column.

Cited by 277 publications

References 25 publications

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis.

Hydrogen Peroxide Induces Topoisomerase I-mediated DNA Damage and Cell Death

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