title: Ziprasidone induces cytotoxicity and genotoxicity in human peripheral lymphocytes.
abstract: It has been stated that some antipsychotic drugs might cause genotoxic and carcinogenic effects. Ziprasidone (ZIP) is commonly used an antipsychotic drug. However, its genotoxicity and carcinogenicity data are very limited. The cytotoxicity and genotoxicity of ZIP on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests in this study. Lymphocyte cultures were treated with 50, 75 and 100 μg/ml of ZIP in the presence and absence of a metabolic activator (S9 mix). Dimethylsulfoxide was used as a solvent control. While the cells were treated with ZIP for 24 h and 48 h in cultures without S9 mix, the cultures with S9 mix were exposed to ZIP for 3 h. ZIP and its metabolites can exert cytotoxic activities due to significant decreases in mitotic index, proliferation index and nuclear division index in the presence and absence of S9 mix. Statistically significant increases in CAs, aberrant cells and MN values in the presence and absence of S9 mix were found in cultures treated with ZIP. While ZIP significantly increased the SCE values in the absence of S9 mix at all concentrations, increased SCE values in cultures with S9 mix were not found to significantly at all concentrations tested. Our results indicated that both ZIP and its metabolites have cytotoxic, cytostatic and genotoxic potential on lymphocyte cultures under the experimental conditions. Further studies are necessary to make a possible risk assessment in patients receiving therapy with this drug.
authors.affiliation: a Department of Biology , Faculty of Science and Letters, Ondokuz Mayıs University , Samsun , Turkey and.
authors.forename: Haluk
authors.initials: H
authors.lastname: Kefelioğlu
authors.affiliation: b Department of Biology , Faculty of Science and Letters, Ordu University , Ordu , Turkey.
authors.forename: Zülal
authors.initials: Z
authors.lastname: Atlı Şekeroğlu
authors.affiliation: a Department of Biology , Faculty of Science and Letters, Ondokuz Mayıs University , Samsun , Turkey and.
authors.forename: Gamze
authors.initials: G
authors.lastname: Coşguner
authors.affiliation: b Department of Biology , Faculty of Science and Letters, Ordu University , Ordu , Turkey.
authors.forename: Seval
authors.initials: S
authors.lastname: Kontaş Yedier
authors.affiliation: b Department of Biology , Faculty of Science and Letters, Ordu University , Ordu , Turkey.
authors.forename: Vedat
authors.initials: V
authors.lastname: Şekeroğlu
mesh_terms: D065767:Activation, Metabolic; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000378:metabolism; D048750:Cell Nucleus Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D015162:Micronucleus Tests; D008862:Microsomes, Liver / Q000201:enzymology; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009153:Mutagens / Q000009:adverse effects*; D010879:Piperazines / Q000009:adverse effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013844:Thiazoles / Q000009:adverse effects* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D009153:Mutagens; D010879:Piperazines; D012702:Serotonin Antagonists; D013844:Thiazoles; C092292:ziprasidone
keywords: Ziprasidone; chromosome aberration; cytotoxicity; lymphocytes; metabolic activation; micronucleus; sister chromatid exchange