Kefelioğlu Haluk, Atlı Şekeroğlu Zülal, Coşguner Gamze, Kontaş Yedier Seval, Şekeroğlu Vedat
a Department of Biology , Faculty of Science and Letters, Ondokuz Mayıs University , Samsun , Turkey and.
b Department of Biology , Faculty of Science and Letters, Ordu University , Ordu , Turkey.
Drug Chem Toxicol. 2017 Oct;40(4):425-431. doi: 10.1080/01480545.2016.1252920. Epub 2016 Nov 29.
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.
据说一些抗精神病药物可能会导致基因毒性和致癌作用。齐拉西酮（ZIP）是一种常用的抗精神病药物。然而，其基因毒性和致癌性数据非常有限。本研究通过姐妹染色单体交换（SCE）、染色体畸变（CA）和微核（MN）试验在体外检测了ZIP对人外周血淋巴细胞的细胞毒性和基因毒性。在有和没有代谢激活剂（S9混合物）的情况下，用50、75和100μg/ml的ZIP处理淋巴细胞培养物。二甲基亚砜用作溶剂对照。在没有S9混合物的培养物中，细胞用ZIP处理24小时和48小时，而有S9混合物的培养物则暴露于ZIP 3小时。无论有无S9混合物，ZIP及其代谢产物均可因有丝分裂指数、增殖指数和核分裂指数显著降低而发挥细胞毒性活性。在用ZIP处理的培养物中，无论有无S9混合物，均发现CA、异常细胞和MN值有统计学意义的增加。在没有S9混合物的情况下，ZIP在所有浓度下均显著增加SCE值，而在有S9混合物的培养物中，在所有测试浓度下均未发现SCE值有显著增加。我们的结果表明，在实验条件下，ZIP及其代谢产物对淋巴细胞培养物均具有细胞毒性、细胞生长抑制性和基因毒性潜力。有必要进行进一步研究，以便对接受该药物治疗的患者进行可能的风险评估。
