Genotoxic effects of prozac and paxil used as antidepressan drug on human lymphocytes culture

GENOTOXIC EFFECTS OF PROZAC AND PAXIL USED ASANTIDEPRESSAN DRUG ON HUMAN LYMPHOCYTES CULTURE(M.Sc. Thesis)Gökçe Hilal TARHANGAZI UNIVERSITYINSTITUTE OF SCIENCE AND TECHNOLOGYSeptember 2006ABSTRACTPaxil and Prozac are two drugs used in the treatment of psychiatric disorders.Prozac and its active ingredient fluoxetine hydrochloride were evaluated usingthree genetic endpoints; 1) chromosomal aberrations (CAs), 2) sister chromatidexchanges (SCEs) and 3) Micronucleus (MN). Prozac and fluoxetinehydrochloride were used at final concentrations of 1.25, 2.50, 5.00 and 10.00µg/ml for the treatment of human peripheral lymphocytes in vitro for 24 h and48 h. All the treatment concentrations in both treatment times increased thefrequency of CAs in a dose dependent manner (in Prozac, r=0.86 for 24 h andr=0.85 for 48 h. in fluoxetine hydrochloride, r=0.90 for 24 h and r=0.90 for 48h). Most frequent type of aberrations were chromatid breaks, dicentricchromosomes and sister unions for both drugs. Prozac and fluoxetinhydrochloride significantly increased SCE frequency dose- dependently in bothtreatment times (in Prozac, r=0.92 for 24 h and r=0.97 for 48 h; in fluoxetinehydrochloride, r=0.92 for 24 h and r=0.98 for 48 h). Both chemicals alsoincreased the number of micronuclei per cell in a dose dependent manner(r=0.98 for Prozac, r=0.99 for fluoxetine hydrochloride). Prozac and fluoxetinehydrochloride significantly decreased mitotic index at both treatment times in adose dependent manner (in Prozac, r=-0.95 for 24 h and r=-0.80 for 48 h; influoxetine hydrochloride, r=-0.95 for 24 h and r=-0.76 for 48 h). Prozac andfluoxetine hydrochloride did not affect replicative index. In the second part ofthis study, lymphocytes from Prozac and Paxil treated patients were examinedusing three genetic endpoints mentioned above. No statistically significantincrease was found in the number of chromosomal aberrations in Prozac andPaxil treated patients. The number of CA/cell statistically increased in patientsin 30-39 age group treated with Prozac and in 20-29 age group treated withPaxil. The number of SCE/cell increased in all age groups in patients treatedwith Prozac and Paxil. MN assay did not show significant differences betweenexposed and control groups. Mitotic index was significantly decreased in Prozactreated patients in age group of 20-29 and, in Paxil treated patients in age groupof 30-39. Replication index did not show significant differences between exposedand control groups. In this study significant differences in CA, SCE, MI andMN frequency between exposed and control groups indicate that Prozac andfluoxetine hydrochloride are clastogenic, cytotoxic, mutagenic and aneugenic incultured human lymphocytes. In patient treated with Prozac and Paxil only thenumber of SCE/cell increased significantly compared with their controls.Science Code : 203.1.048Key Words : Prozac, fluoxetine hydrochloride, Paxil, humanlymphocyte culture, genotoxic effects, chromosomalaberrations (CAs), sister chromatid exchanges (SCEs),mitotic index (MI), micronuclei (MN).Page Number : 72Adviser : Prof. Dr. Fatma ÜNAL