of work: Studies have demonstrated that several cellular markers of oxidative stress are higher in cells from Alzheimer disease (AD) patients as compared to normal age- matched controls. These markers include oxidative damage to lipids, proteins, and DNA in various tissues from AD patients. It has been proposed that AD cells may have a defect in the DNA repair processing of oxidative base lesion leading to accumulation of DNA damage in AD cells. We have investigated the repair of oxidative base lesions using whole cell extracts from cultured AD lymphoblasts. DNA substrates containing both pyrimidine and purine lesions were obtained by treatment of plasmid with either gamma irradiation or fluorescent light (FL). Plasmid DNA containing primarily thymine glycol or 8- hydroxyguanine was prepared by damaging DNA with either OsO4 or methylene blue plus light ,respectively. The DNA substrates were purified free of strand breaks and were used in DNA repair synthesis assays. FAD cells were proficient in repair of these substrates containing various oxidative base lesions. Extracts from FAD cells repaired the plasmids damaged by gamma or FL- irradiation with equal efficiency as extracts from unaffected individuals. Furthermore, DNA damaged with methylene blue plus light and OsO4 were repaired with greater efficiency using FAD extracts (approximately 0.5-fold increase) as compared to cells from unaffected individuals. Our data indicate that the DNA damages resulting from the oxidative stresses used here are repaired efficiently in FAD cells. It is possible that the repair of specific oxidative base damages, such as that seen for thymine glycol and 8-hydroxyguanine, may be upregulated in FAD due to chronic oxidative stress which has been previously implicated in this disease. Additionally, there have been reports of unusual accummulation of oxidative DNA damage in mitochondrial DNA from patients with AD, and we are have recently developed novel techniques to study DNA repair in these organelles. We thus plan to investigate the DNA repair efficiency in mitochondrai from individuals with AD.
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