Assessment of DNA damage in C6 glioma cells after antidepressant treatment using an alkaline comet assay.
The effects of acute (24 h) exposure to the antidepressants amitriptyline, imipramine (both tricyclics), fluoxetine (a selective serotonin re-uptake inhibitor) and tranylcypromine (a monoamine oxidase inhibitor) on DNA damage in cultured C6 rat glioma cells were determined using an alkaline comet assay. The effects of manipulation of intracellular cyclic AMP by pretreatment with dibutyryl cyclic AMP (dBcAMP) and 3-isobutyl-1-methylxanthine (IBMX) were also studied. For fluoxetine, the effects of addition of exogenous glutathione (GSH) and pretreatment with L-buthionine sulfoximine (BSO) were also assessed. There were increases in DNA damage with increasing concentrations of antidepressants. IBMX pretreatment protected against antidepressant-induced DNA damage in C6 cells pretreated with dBcAMP. Addition of exogenous reduced GSH and BSO increased DNA damage after fluoxetine exposure. The data show that the antidepressants induce significant amounts DNA damage in C6 cells.
Slamon
N D
ND
Department of Biological Sciences, University of Salford, UK.
Ward
T H
TH
Butler
J
J
Pentreath
V W
VW
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000633:toxicity*; D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D003994:Bucladesine / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D020552:Comet Assay; D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma; D005978:Glutathione / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D019328:Buthionine Sulfoximine; D003994:Bucladesine; D005978:Glutathione; D015056:1-Methyl-3-isobutylxanthine