Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-18911
Stopper, H; Schupp, N; Fazeli, G; Dietel, B; Queisser, N; Walitza, S; Gerlach, M (2009). Genotoxicity of the neurotransmitter dopamine in vitro. Toxicology in vitro, 23(4):640-646.
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Alterations in dopamine levels play a role in several human pathological conditions and their pharmacological treatment. Here we describe an induction of genomic damage detected as micronucleus formation by concentrations in the low micromolar range (6.25-25muM) in three cell lines in vitro. Rat neuronal PC12 cells exhibited a more pronounced induction (about 10-fold over control at 100muM) than human lymphoblastoid TK6 cells and rat kidney NRK cells (about 2-fold over control at 100muM). The role of transporters and receptors in the formation of genomic damage was investigated in PC12 cells, in which the effect of dopamine was reduced by addition of the antioxidants TEMPOL and dimethylthiourea, by inhibitors of the dopamine transporter (GBR 12909 and nomifensine) and by a D2 antagonist (sulpiride). Antioxidative effects of nomifensine and sulpiride, but not of GBR 12909, were excluded, since they did not protect oxidative stress sensitive HL-60 cells from hydrogen peroxide-induced damage in the comet assay. Thus, the transport of dopamine into the cell and the signalling upon binding to D2 receptors was required for the genotoxic effect of dopamine in PC12 cells, which was mediated by intracellular dopamine oxidation products and/or reactive oxygen species.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Child and Adolescent Psychiatry|
|DDC:||610 Medicine & health|
|Date:||28 October 2009|
|Deposited On:||08 Jun 2009 10:33|
|Last Modified:||08 Mar 2013 15:58|
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