title: Impact of psychostimulants and atomoxetine on the expression of 8-hydroxyguanine glycosylase 1 in human cells.
abstract: Oxidative DNA damage as one sign of reactive oxygen species induced oxidative stress is an important factor in the pathogenesis of various psychiatric disorders. Altered levels of DNA base damage products as well as the expression of the main repair enzyme 8-hydroxyguanine glycosylase 1 have been described. The aim of the present study was to examine the effects of drugs (amphetamine, methylphenidate and atomoxetine) used in the treatment of attention deficit-hyperactivity disorder on the expression of this enzyme via reverse transcriptase-polymerase chain reaction in human neuroblastoma SH-SY5Y and human monocytic U-937 cells at concentrations of 50, 500 and 5,000 ng/ml. We observed decreased expression of this enzyme for all applied substances. In U-937 cells, the significance level was reached after treatment with 5,000 ng/ml amphetamine as well as after treatment with 50, 500 and 5,000 ng/ml atomoxetine. Incubation of SH-SY5Y cells with 50 and 5,000 ng/ml amphetamine and 5,000 ng/ml methylphenidate led to significant decreases of 8-hydroxyguanine glycosylase 1. As a positive correlation between the expression of 8-hydroxyguanine glycosylase 1 and the level of oxidative DNA damage products has been described, we accordingly consider these substances (amphetamine, methylphenidate and atomoxetine) to possibly play a protective role in this process.
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps-University, Marburg, Rudolf-Bultmann-Strasse 8, 35033 Marburg, Germany. andreasschmidt.marburg@freenet.de
authors.forename: Andreas Johannes
authors.initials: AJ
authors.lastname: Schmidt
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Clement
authors.forename: Stefan
authors.initials: S
authors.lastname: Gebhardt
authors.forename: Ulrich Michael
authors.initials: UM
authors.lastname: Hemmeter
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schulz
authors.forename: Jürgen-Christian
authors.initials: JC
authors.lastname: Krieg
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
authors.forename: Philip
authors.initials: P
authors.lastname: Heiser
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology; D000069445:Atomoxetine Hydrochloride; D002460:Cell Line; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008774:Methylphenidate / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology; D009447:Neuroblastoma; D011437:Propylamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D011437:Propylamines; D012333:RNA, Messenger; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D000661:Amphetamine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human
references.citation: Toxicol Lett. 2009 Jan 10;184(1):38-43
references.pmid: 19015014
references.citation: Psychiatry Res. 2007 Sep 30;153(1):27-32
references.pmid: 17582509
references.citation: Neurobiol Aging. 2005 May;26(5):567-73
references.pmid: 15708428
references.citation: Am J Geriatr Psychiatry. 2004 Mar-Apr;12(2):167-75
references.pmid: 15010346
references.citation: Biol Psychol. 2008 Oct;79(2):256-9
references.pmid: 18644422
references.citation: J Neural Transm (Vienna). 2006 Dec;113(12):1927-34
references.pmid: 16736241
references.citation: World J Gastroenterol. 2003 Oct;9(10):2186-93
references.pmid: 14562375
references.citation: J Neurochem. 2005 May;93(4):953-62
references.pmid: 15857398
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2008 Jul-Aug;79(1-2):47-53
references.pmid: 18757191
references.citation: Cancer Lett. 2005 Dec 18;230(2):284-91
references.pmid: 16297714
references.citation: J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009 Apr;27(2):120-39
references.pmid: 19412858
references.citation: J Neurochem. 1999 Feb;72(2):771-6
references.pmid: 9930752
references.citation: J Neural Transm (Vienna). 2008;115(2):331-4
references.pmid: 17994183
references.citation: J Psychiatr Res. 2005 Nov;39(6):553-60
references.pmid: 16005897
references.citation: Environ Health Perspect. 2007 Jun;115(6):936-40
references.pmid: 17589603
references.citation: Leuk Res. 2007 Mar;31(3):387-93
references.pmid: 16949154
references.citation: Free Radic Biol Med. 2005 Aug 1;39(3):317-26
references.pmid: 15993330
references.citation: Psychosom Med. 2006 Jan-Feb;68(1):1-7
references.pmid: 16449405
references.citation: Free Radic Biol Med. 1991;10(3-4):225-42
references.pmid: 1650738
references.citation: Free Radic Biol Med. 2002 Jul 15;33(2):192-200
references.pmid: 12106815
references.citation: J Psychopharmacol. 2010 Dec;24(12):1829-33
references.pmid: 19605603
references.citation: J Psychiatr Res. 2006 Jun;40(4):374-9
references.pmid: 16002093
references.citation: Free Radic Res. 2006 Sep;40(9):1003-10
references.pmid: 17015282
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 15;31(6):1282-8
references.pmid: 17614179