Thymine hydroperoxide as a potential source of singlet molecular oxygen in DNA
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2009
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Resumo |
The decomposition of organic hydroperoxides into peroxyl radicals is a potential source of singlet molecular oxygen [O(2) ((1)Delta(g))] in biological systems. This study shows that 5-(hydroperoxymethyl)uracil (5-HPMU), a thymine hydroperoxide within DNA, reacts with metal ions or HOCl, generating O(2) ((1)Delta(g)). Spectroscopic evidence for generation of O(2) ((1)Delta(g)) was obtained by measuring (i) the bimolecular decay, (ii) the monomolecular decay, and (iii) the observation of D(2)O enhancement of O(2) ((1)Delta(g)) production and the quenching effect of NaN(3). Moreover, the presence of O(2) ((1)Delta(g)) was unequivocally demonstrated by the direct characterization of the near-infrared light emission. For the sake of comparison, O(2) ((1)Delta(g)) derived from the H(2)O(2)/HOCl system and from the thermolysis of the N,N`-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide endoperoxide was also monitored. More evidence of O(2) ((1)Delta(g)) generation was obtained by chemical trapping of O(2) ((1)Delta(g)) with anthracene-9,10-divinylsulfonate (AVS) and detection of the specific AVS endoperoxide by HPLC/MS/MS. The detection by HPLC/MS of 5-(hydroxymethyl)uracil and 5-formyluracil, two thymine oxidation products generated from the reaction of 5-HPMU and Ce(4+) ions, supports the Russell mechanism. These photoemission properties and chemical trapping clearly demonstrate that the decomposition of 5-HPMU generates O(2) ((1)Delta(g)) by the Russell mechanism and point to the involvement of O(2) ((1)Delta(g)) in thymidine hydroperoxide cytotoxicity. (C) 2009 Elsevier Inc. All rights reserved. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico (CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Instituto do Milenio: Redoxoma Instituto do Milenio: Redoxoma INCT de Processos Redox em Biomedicina-Redoxoma INCT de Processos Redox em Biomedicina-Redoxoma Universidade de São Paulo - Pro-reitoria de Pesquisa da USP Universidade de São Paulo - Pro-reitoria de Pesquisa da USP |
Identificador |
FREE RADICAL BIOLOGY AND MEDICINE, v.47, n.4, p.401-409, 2009 0891-5849 http://producao.usp.br/handle/BDPI/30820 10.1016/j.freeradbiomed.2009.05.001 |
Idioma(s) |
eng |
Publicador |
ELSEVIER SCIENCE INC |
Relação |
Free Radical Biology and Medicine |
Direitos |
restrictedAccess Copyright ELSEVIER SCIENCE INC |
Palavras-Chave | #Singlet molecular oxygen #5-(Hydroperoxymethyl)uracil #Thymine hydroperoxide #Near-infrared emission #HPLC/MS/MS #Chemiluminescence #Chemical trapping #Free radicals #LINOLEIC-ACID HYDROPEROXIDE #LIGHT-EMISSION MEASUREMENTS #HYPOCHLOROUS ACID #NUCLEOSIDE 2`-DEOXYGUANOSINE #MECHANISTIC INSIGHTS #OXIDATION-PRODUCTS #O-2 ((1)DELTA(G)) #MASS-SPECTROMETRY #RUSSELL MECHANISM #AQUEOUS-SOLUTION #Biochemistry & Molecular Biology #Endocrinology & Metabolism |
Tipo |
article original article publishedVersion |