Reevaluating the role of 1,10-phenanthroline in oxidative reactions involving ferrous ions and DNA damage

被引:94
作者
de Avelar, IGJ
Magalhaes, MMM
Silva, AB
Souza, LL
Leitao, AC [1 ]
Hermes-Lima, M
机构
[1] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Radiobiol Mol, BR-21949900 Rio De Janeiro, Brazil
[2] Univ Brasilia, Dept Biol Celular, Oxyrad Res Grp, BR-70910900 Brasilia, DF, Brazil
[3] Univ Brasilia, Inst Quim, BR-70910900 Brasilia, DF, Brazil
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2004年 / 1675卷 / 1-3期
关键词
iron; 1,10-phenanthroline; Fe(phen)(2)(+)(3); hydroxyl radical; DNA breakage; oxidative stress;
D O I
10.1016/j.bbagen.2004.08.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It is widely believed that the iron chelator 1,10-phenanthroline (phen) is able to fully block the Fenton reaction by forming a complex (Fe(phen)(3)(2+), also known as ferroin) that cannot react with H2O2. We observed that phen cannot fully prevent 2-deoxyribose (5 mM) degradation induced by Fenton reagents (30 muM Fe(II) plus 100-500 muM H2O2); protection varied from 55% to 66% when the phen/Fe(II) ratio was 3:1 to 20:1. Inhibition of 2-deoxyribose damage was nearly unchanged if phen was pre-incubated with Fe(II). Moreover, preformed Fe(phen)(3)(2+) complex added to the solution containing H2O2 was able to induce 2-deoxyribose degradation and methane sulfinic acid formation from the oxidation of 5% DMSO. The partially protective effect of phen was unchanged with the use of either phosphate or HEPES as buffers (5 mM, pH 7.2), or in unbuffered media (pH 5.1). Both DMSO oxidation and 2-deoxyribose degradation correlated with the increase in Fe(phen)(3)(2+) concentration. Strand breaks in plasmid pTARGET(TM) DNA induced by Fenton reagents (1 muM Fe(II) plus 25 muM H2O2) in HEPES buffer could only be partially prevented by phen, even when the chelator was 16 times more concentrated than Fe(II). In these experiments, Fe(phen)(3)(2+) and DNA were pre-incubated from 1 to 10 min before addition of H2O2.. Moreover, a high level of DNA strand breakage was observed when iron and phen are added to the reaction immediately before H2O2. On the other hand, phen fully prevented 2-deoxyribose degradation induced by the autoxidation of 30 muM Fe(II) in phosphate-buffered (3 to 30 mM) media. Our data provide evidence that the Fe(phen)(3)(2+) complex induces in vitro oxidative damage in the presence of H2O2 (possibly by means of Fe(phen)(3)(2+) dissociation into Fe(phen)(3)(2+)), but they show that the complex cannot undergo autoxidation. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:46 / 53
页数:8
相关论文
共 27 条
  • [21] 3 CHEMICALLY DISTINCT TYPES OF OXIDANTS FORMED BY IRON-MEDIATED FENTON REACTIONS IN THE PRESENCE OF DNA
    LUO, YZ
    HAN, ZX
    CHIN, SM
    LINN, S
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (26) : 12438 - 12442
  • [22] Pyridoxal isonicotinoyl hydrazone inhibits iron-induced ascorbate oxidation and ascorbyl radical formation
    Maurício, AQ
    Lopes, GKB
    Gomes, CS
    Oliveira, RG
    Alonso, A
    Hermes-Lima, M
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2003, 1620 (1-3): : 15 - 24
  • [23] MELLOFILHO AC, 1985, BIOCHIM BIOPHYS ACTA, V847, P82
  • [24] Iron homeostasis, oxidative stress, and DNA damage
    Meneghini, R
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1997, 23 (05) : 783 - 792
  • [25] Iron and dioxygen chemistry is an important route to initiation of biological free radical oxidations: An electron paramagnetic resonance spin trapping study
    Qian, SY
    Buettner, GR
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1999, 26 (11-12) : 1447 - 1456
  • [26] CHARACTERISTICS OF AN OXIDANT FORMED DURING IRON(II) AUTOXIDATION
    REINKE, LA
    RAU, JM
    MCCAY, PB
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1994, 16 (04) : 485 - 492
  • [27] Iron autoxidation and free radical generation: Effects of buffers, ligands, and chelators
    Welch, KD
    Davis, TZ
    Aust, SD
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2002, 397 (02) : 360 - 369