Impact of psychostimulants and atomoxetine on the expression of 8-hydroxyguanine glycosylase 1 in human cells.
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.
Schmidt
Andreas Johannes
AJ
Department of Psychiatry and Psychotherapy, Philipps-University, Marburg, Rudolf-Bultmann-Strasse 8, 35033 Marburg, Germany. andreasschmidt.marburg@freenet.de
Clement
Hans-Willi
HW
Gebhardt
Stefan
S
Hemmeter
Ulrich Michael
UM
Schulz
Eberhard
E
Krieg
Jürgen-Christian
JC
Kircher
Tilo
T
Heiser
Philip
P
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
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
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