Elevated levels of oxidative DNA damage in lymphocytes from patients with Alzheimer's disease

被引:103
作者
Mórocz, M
Kálmán, J
Juhász, A
Sinkó, I
McGlynn, AP
Downes, CS
Janka, Z
Raskó, I
机构
[1] Hungarian Acad Sci, Biol Res Ctr, Inst Genet, H-6701 Szeged, Hungary
[2] Univ Szeged, Fac Med, Albert Szent Gyorgyi Ctr Med & Pharmaceut Sci, Dept Psychiat, H-6725 Szeged, Hungary
[3] Univ Ulster, Sch Biomed Sci, Canc & Aging Res Grp, Coleraine BT52 1SA, Londonderry, North Ireland
关键词
Alzheimer's disease; lymphocytes; oxidative stress; Comet assay; DNA-repair;
D O I
10.1016/S0197-4580(01)00257-3
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Previous studies have provided evidence of the involvement of oxidative damage in the pathogenesis of Alzheimer's disease (AD). Although the role of oxidative stress in the aetiology of the disease is still not clear, the detection of an increased damage status in the cells of patients could have important therapeutic implications. The level of oxidative damage and repair capacity in peripheral lymphocytes of AD patients and of age-matched controls was determined by the Comet assay applied to freshly isolated blood samples with oxidative lesion-specific DNA repair endonucleases. This is less prone to errors arising from oxidative artifacts than chemical analytical methods; and is therefore a relatively reliable, as well as rapid method for assay of oxidative DNA damage in cells. Statistically significant elevations (P < 0.05) of oxidized purines were observed in nuclear DNA of peripheral lymphocytes from AD patients, compared. to age matched control subjects, both at basal level and after oxidative stress induced by H2O2. AD patients also showed a diminished repair of H2O2 -induced oxidized purines. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:47 / 53
页数:7
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共 47 条
  • [11] The comet assay: What can it really tell us?
    Collins, AR
    Dobson, VL
    Dusinska, M
    Kennedy, G
    Stetina, R
    [J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1997, 375 (02) : 183 - 193
  • [12] THE KINETICS OF REPAIR OF OXIDATIVE DNA-DAMAGE (STRAND BREAKS AND OXIDIZED PYRIMIDINES) IN HUMAN-CELLS
    COLLINS, AR
    MA, AG
    DUTHIE, SJ
    [J]. MUTATION RESEARCH-DNA REPAIR, 1995, 336 (01): : 69 - 77
  • [13] Oxidative damage to DNA: Do we have a reliable biomarker?
    Collins, AR
    Dusinska, M
    Gedik, CM
    Stetina, R
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 1996, 104 : 465 - 469
  • [14] ANALYSES OF MITOCHONDRIAL RESPIRATORY-CHAIN FUNCTION AND MITOCHONDRIAL-DNA DELETION IN HUMAN SKELETAL-MUSCLE - EFFECT OF AGING
    COOPER, JM
    MANN, VM
    SCHAPIRA, AHV
    [J]. JOURNAL OF THE NEUROLOGICAL SCIENCES, 1992, 113 (01) : 91 - 98
  • [15] Oxidative metabolism in cultured fibroblasts derived from sporadic Alzheimer's disease (AD) patients
    Curti, D
    Rognoni, F
    Gasparini, L
    Cattaneo, A
    Paolillo, M
    Racchi, M
    Zani, L
    Bianchetti, A
    Trabucchi, M
    Bergamaschi, S
    Govoni, S
    [J]. NEUROSCIENCE LETTERS, 1997, 236 (01) : 13 - 16
  • [16] OXIDATIVE DAMAGE TO DNA IN MAMMALIAN CHROMATIN
    DIZDAROGLU, M
    [J]. MUTATION RESEARCH, 1992, 275 (3-6): : 331 - 342
  • [17] THE COMET ASSAY - A COMPREHENSIVE REVIEW
    FAIRBAIRN, DW
    OLIVE, PL
    ONEILL, KL
    [J]. MUTATION RESEARCH-REVIEWS IN GENETIC TOXICOLOGY, 1995, 339 (01): : 37 - 59
  • [18] REVIEW OF REPAIR KINETICS FOR DNA DAMAGE INDUCED IN EUKARYOTIC CELLS-INVITRO BY IONIZING-RADIATION
    FRANKENBERGSCHWAGER, M
    [J]. RADIOTHERAPY AND ONCOLOGY, 1989, 14 (04) : 307 - 320
  • [19] Increased nuclear DNA oxidation in the brain in Alzheimer's disease
    Gabbita, SP
    Lovell, MA
    Markesbery, WR
    [J]. JOURNAL OF NEUROCHEMISTRY, 1998, 71 (05) : 2034 - 2040
  • [20] Measuring oxidative damage to DNA; HPLC and the comet assay compared
    Gedik, CM
    Wood, SG
    Collins, AR
    [J]. FREE RADICAL RESEARCH, 1998, 29 (06) : 609 - 615