Investigation of the genotoxic acti̇vi̇ty of fluoxeti̇ne hydrochlori̇de used i̇n the treartment of depressi̇on and anxi̇ent di̇sorder by in vitro methods

Genotoxicity is the direct and indirect toxicity of cells to their genetic material. Since most of the drugs have mutagenic, genotoxic and clastogenic side effects, it is very important to investigate the benefits and harms of drug therapy for a long time. In this thesis, the genotoxic effect of different doses of Fluoxetine hydrochloride (6,8.10 and 12 µg/mL), an antidepressant widely used in the world, on human peripheral lymphocytes was investigated by the Cytokinesis-Blocked Micronucleus test (CBMN) and the Comet test in vitro. According to the data obtained from the CBMN test, the cell proliferation index (CPI) showed a significant difference compared to control group only at the highest dose (12 μg/mL) at 24 hours exposure and at 10 and 12 μg/mL doses at 48 hours exposure. In terms of the amount of MN, it showed a significant difference compared to the control group at 24 and 48 hours of exposure depending on the dose and time. According to the data obtained by Comet test, high doses of fluoxetine hydrochloride showed statistically significant differences with the negative control group in terms of tail length, tail moment and tail density, which are DNA damage parameters. As a result of this study, it was concluded that Fluoxetine hydrochloride may show genotoxic, cytotoxic and cytostatic effects in human lymphocyte cells depending on the increase in dose amount and exposure time. It is recommended that these results be confirmed by studies using various in vivo and in vitro methods.