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)

Exposure of the plasmid pBR 322 to the aerobic xanthine oxidase reaction introduced single strand scissions and endonuclease III-sensitive sites. The latter may be residues of thymine glycol. Both forms of DNA damage were completely prevented by superoxide dismutase or catalase, whereas bovine serum albumin was much less effective. Mannitol and benzoate, added as scavengers of HO., and desferrioxamine or diethylene triamine pentaacetate, added to sequester Fe(III), also protected. These results indicate a metal-catalyzed interaction of O2- with H2O2, which produces HO. which, in turn, causes DNA strand scission and oxidation of thymine residues to thymine glycol. Plasmid isolated from aerobically-incubated cells contained more strand scissions and endonuclease III-sensitive sites than did plasmid from anaerobically-incubated cells, and a low molecular weight scavenger of O2- prevented the damage seen with the aerobic cells. Genetic defects in AP endonucleases rendered E. coli more susceptible to the dioxygen-dependent lethality of plumbagin, which mediates O2- production. Similarly, plasmid DNA, within the endonuclease-deficient cells, exhibited more strand scissions and endonuclease III-sensitive sites upon aerobic exposure to plumbagin than did endonuclease-sufficient cells, and a low molecular weight scavenger of O2- was protective. These results are consistent with the conclusions that strand scissions and formation of endonuclease III-sensitive sites are among the consequences of exposure of DNA to O2- plus H2O2, both in vitro and in vivo.
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PMID:Formation of endonuclease III-sensitive sites as a consequence of oxygen radical attack on DNA. 254 64

When irradiated at 360 nm, furocoumarins with a hydroperoxide group in a side chain efficiently give rise to a type of DNA damage that can best be explained by a photo-induced generation of hydroxyl radicals from the excited photosensitizers. The observed DNA damage profiles, i.e. the ratios of single-strand breaks, sites of base loss (AP sites) and base modifications sensitive to formamidopyrimidine--DNA glycosylase (FPG protein) and endonuclease III, are similar to the DNA damage profile produced by hydroxyl radicals generated by ionizing radiation or by xanthine and xanthine oxidase in the presence of Fe(III)--EDTA. No such damage is observed with the corresponding furocoumarin alcohols or in the absence of near-UV radiation. The damage caused by the photo-excited hydroperoxides is not influenced by superoxide dismutase (SOD) or catalase or by D2O as solvent. The presence of t-butanol, however, reduces both the formation of single-strand breaks and of base modifications sensitive to FPG protein. The cytotoxicity caused by one of the hydroperoxides in L5178Y mouse lymphoma cells is found to be dependent on the near-UV irradiation and to be much higher than that of the corresponding alcohol. Therefore the new type of photo-induced damage occurs inside cells. Intercalating photosensitizers with an attached hydroperoxide group might represent a novel and versatile class of DNA damaging agents, e.g. for phototherapy.
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PMID:DNA damage induced by furocoumarin hydroperoxides plus UV (360 nm). 824 54

This study was designed to investigate the repair of oxidative damage in nuclear DNA sequences with different transcriptional activities. Chinese hamster ovary (CHO) cells were treated with the oxygen radical generator hypoxanthine/xanthine oxidase (Hyp/XO). Damage and repair were evaluated in 14-kb restriction fragments containing either the DHFR gene, a 3'-non-transcribed flanking region, or the c-fos gene using a quantitative Southern blot technique. Damage to the sugar-phosphate backbone and abasic sites were detected by measuring their lability in alkali conditions. Lesions in DNA bases were identified using the bacterial repair enzyme endonuclease III, which predominantly recognizes damage to thymines and cytosines, and formamidopyrimidine-DNA glycosylase, which recognizes 8-oxoguanine and purines with fractured imidazole rings. The results showed that similar amounts of all types of oxidative damage were produced in both the transcribed and non-transcribed sequences following a 1-h exposure to the radical generator. Repair in all sequences was rapid, with approximately 60% removal of lesions observed by 1 h. Therefore, within these sequences, the repair of oxidative lesions is much faster than that of other types of damage, such as those induced by alkylating toxins and UV irradiation, and the repair is not affected appreciably by transcriptional status.
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PMID:Repair of oxidative damage in nuclear DNA sequences with different transcriptional activities. 929 16

Low birth weight and accelerated postnatal growth lead to increased risk of cardiovascular disease. We reported previously that rats exposed to a low-protein diet in utero and postnatal catch-up growth (recuperated) develop metabolic dysfunction and have reduced life span. Here we explored the hypothesis that cardiac oxidative and nitrosative stress leading to DNA damage and accelerated cellular aging could contribute to these phenotypes. Recuperated animals had a low birth weight (P<0.001) but caught up in weight to controls during lactation. At weaning, recuperated cardiac tissue had increased (P<0.05) protein nitrotyrosination and DNA single-stranded breaks. This condition was preceded by increased expression of DNA damage repair molecules 8-oxoguanine-DNA-glycosylase-1, nei-endonuclease-VIII-like, X-ray-repair-complementing-defective-repair-1, and Nthl endonuclease III-like-1 on d 3. These differences were maintained on d 22 and became more pronounced in the case of 8-oxoguanine-DNA-glycosylase-1 and nei-endonuclease-VIII-like. This was accompanied by increases in xanthine oxidase (P<0.001) and NADPH oxidase (P<0.05), major sources of reactive oxygen species (ROS). The detrimental effects of increased ROS in recuperated offspring may be exaggerated at 22 d by reductions (P<0.001) in the antioxidant enzymes peroxiredoxin-3 and CuZn-superoxide-dismutase. We conclude that poor fetal nutrition followed by accelerated postnatal growth results in increased cardiac nitrosative and oxidative-stress and DNA damage, which could contribute to age-associated disease risk.
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PMID:Poor maternal nutrition followed by accelerated postnatal growth leads to alterations in DNA damage and repair, oxidative and nitrosative stress, and oxidative defense capacity in rat heart. 2302 73