Detection of dopamine--DNA adducts: potential role in Parkinson's disease.
Oxidation of catecholamines may lead to the formation of o-semiquinones and o-quinones in catecholaminergic brain tissues, and these reactive molecules may form DNA or protein adducts. In this study, cultured cells were treated with dopamine (DA) for 24 h and 32P-postlabelling was used to detect DA-DNA adducts. In HL-60 cells, 250 microM DA induced 8.5 DNA adducts/10(8) nucleotides; adduct formation was dose-dependent up to 500 microM DA. Addition of H2O2 increased the relative adduct levels 7- to 13-fold, but no adducts were detected when DA and ascorbic acid were added simultaneously. In human glioblastoma cell lines U87, U251, SF-763 and SF-767, 1000 microM DA produced 0.98-2.31 adducts/10(8) nucleotides. These results suggest that the formation of DNA adducts by DA may contribute to the development of certain neurodegenerative diseases such as Parkinson's disease.
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
G
G
Lévay
W J
WJ
Bodell
D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004247:DNA; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; D004298:Dopamine