Elevated levels of oxidative DNA damage in lymphocytes from patients with Alzheimer's disease.
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 H(2)O(2.) AD patients also showed a diminished repair of H(2)O(2) -induced oxidized purines.
Mórocz
Mónika
M
Biological Research Centre of Hungarian Academy of Sciences, Institute of Genetics, POB 521, H-6701, Szeged, Hungary. morocz@nucleus.szbk.u-szeged.hu
Kálmán
János
J
Juhász
Anna
A
Sinkó
Ildikó
I
McGlynn
Angela P
AP
Downes
C Stephen
CS
Janka
Zoltán
Z
Raskó
István
I
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D043382:DNA-Formamidopyrimidine Glycosylase; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004586:Electrophoresis; D004706:Endodeoxyribonucleases / Q000494:pharmacology; D029968:Escherichia coli Proteins; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D009699:N-Glycosyl Hydrolases / Q000494:pharmacology; D018384:Oxidative Stress; D016610:Tissue Embedding
D029968:Escherichia coli Proteins; D007202:Indicators and Reagents; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase