Detection of dopamine DNA adducts: potential role in Parkinson's disease |
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Authors: | Levay, Gyorgy Bodell, William J. |
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Affiliation: | 1Brain Tumor Research Center of the Department of Neurological Surgery San Francisco, CA 94143, USA 2Department of Radiation Oncology, School of Medicine, University of California San Francisco, CA 94143, USA |
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Abstract: | Oxidation of catecholamines may lead to the formation of O-semiquinonesand o-quinones in catecholaminergic brain tissues, and thesereactive molecules may form DNA or protein adducts. In thisstudy, cultured cells were treated with dopamine (DA) for 24h and 32P-postlabeling was used to detect DA-DNA adducts. InHL60 cells, 250µM DA induced 8.5 DNA adducts/108nucleotides; adduct formation was dose-dependent up to 500 µMDA. Addition of H2O2 increased the relative adduct levels 7-to 13-fold, but no adducts were detected when DA and ascorbicacid were added simultaneously. In human glioblastoma cell linesU87, U251, SF-763 and SF-767, 1000 µM DA produced 0.982.31adducts/108 nucleotides. These results suggest that the formationof DNA adducts by DA may contribute to the development of certainneurodegenerative diseases such as Parkinson's disease. |
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