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Titolo:
Nitrite-induced deamination and hypochlorite-induced oxidation of DNA in intact human respiratory tract epithelial cells
Autore:
Spencer, JPE; Whiteman, M; Jenner, A; Halliwell, B;
Indirizzi:
Natl Univ Singapore, Dept Biochem, Singapore 119620, Singapore Natl Univ Singapore Singapore Singapore 119620 ngapore 119620, Singapore Univ London Kings Coll, Int Antioxidant Res Ctr, London WC2R 2LS, England Univ London Kings Coll London England WC2R 2LS London WC2R 2LS, England
Titolo Testata:
FREE RADICAL BIOLOGY AND MEDICINE
fascicolo: 7, volume: 28, anno: 2000,
pagine: 1039 - 1050
SICI:
0891-5849(20000401)28:7<1039:NDAHOO>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHROMATOGRAPHY-MASS-SPECTROMETRY; HYDROGEN-PEROXIDE; HUMAN-NEUTROPHILS; BASE MODIFICATION; STRAND BREAKAGE; ACID; DAMAGE; OXIDE; CHLORINATION; GENERATION;
Keywords:
nitrite; nitrogen dioxide; nitrous acid; hypochlorous acid; deamination; xanthine; hypoxanthine; reactive nitrogen species; gastric cancer; lung; free radicals;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Halliwell, B Natl Univ Singapore, Dept Biochem, 10 Kent Ridge Crescent, Singapore 119620, Singapore Natl Univ Singapore 10 Kent Ridge Crescent Singapore Singapore 119620
Citazione:
J.P.E. Spencer et al., "Nitrite-induced deamination and hypochlorite-induced oxidation of DNA in intact human respiratory tract epithelial cells", FREE RAD B, 28(7), 2000, pp. 1039-1050

Abstract

No modification of purine or pyrimidine bases was observed when isolated DNA was incubated with 1 mM nitrite at pH 7.4. However, exposure of human bronchial epithelial cells in culture medium at pH 7.4 to nitrite at concentrations of 100 mu M or greater led to deamination of purine bases in cellular DNA. Deamination was more extensive in cells exposed to lower extracellular pH values and higher nitrite concentrations. Significant increases in the levels of xanthine and hypoxanthine, putative deamination products of guanine and adenine, respectively, were observed in DNA from nitrite-treated cells but no rise in any base oxidation products such as 8-hydroxyguanine. This pattern of damage suggests that exposure of cells to nitrite (even at pH 7.4) leads to intracellular generation of "reactive nitrogen species" capable of deaminating purines in DNA. In addition, significant DNA strand breakage occurred in nitrite-treated cells. The time course of base damage suggested that the repair of deaminated purine lesions in these cells is slow. By contrast, DNA isolated from cells exposed to hypochlorous acid (HOCl) has significant oxidation of pyrimidine bases and chlorination of cytosine but little oxidation of purines. Exposure of cells to both species (NO2- plus HOCl) potentiated the oxidative DNA base damage observed but decreased the extent of deamination. Pie hypothesize that this is due to the formation of nitryl chloride (NO2Cl) from reaction of HOCl with . NO2-. The relevanceof our observations to events in the stomach and respiratory tract, at sites of inflammation, and in ischemic tissues is discussed. (C) 2000 ElsevierScience Inc.

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Documento generato il 27/11/20 alle ore 22:05:39