Assessment of DNA damage in C6 glioma cells after antidepressant treatmentusing an alkaline comet assay

The effects of acute (24 h) exposure to the antidepressants amitriptyline, imipramine (both tricyclics), fluoxetine (a selective serotonin re-uptake i nhibitor) and tranylcypromine (a monoamine oxidase inhibitor) on DNA damage in cultured C6 rat glioma cells were determined using an alkaline comet as say. The effects of manipulation of intracellular cyclic AMP by pretreatmen t with dibutyryl cyclic AMP (dBcAMP) and 3-isobutyl-1-methylxanthine (IBMX) were also studied. For fluoxetine, the effects of addition of exogenous gl utathione (GSH) and pretreatment with L-buthionine sulfoximine (BSO) were a lso assessed. There were increases in DNA damage with increasing concentrat ions of antidepressants. IBMX pretreatment protected against antidepressant -induced DNA damage in C6 cells pretreated with dBcAMP. Addition of exogeno us reduced GSH and BSO increased DNA damage after fluoxetine exposure. The data show that the antide- pressants induce significant amounts DNA damage in C6 cells.