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Detection of dopamine DNA adducts: potential role in Parkinson's disease
Authors:Levay, Gyorgy   Bodell, William J.
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
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. InHL–60 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 0.98–2.31adducts/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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