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.
Lévay
G
G
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
Bodell
W J
WJ
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