Genetic Toxicology Laboratory, Department of Biology, Science Faculty, Gazi University, 06500, Teknikokullar, Ankara, Turkey.
Genetic Toxicology Laboratory, Department of Biology, Science Faculty, Gazi University, 06500, Teknikokullar, Ankara, Turkey.
Food Chem Toxicol. 2018 Feb;112:235-241. doi: 10.1016/j.fct.2018.01.003. Epub 2018 Jan 6.
Sitagliptin is an active ingredient of antidiabetic drug used in the treatment of type 2 diabetes mellitus (T2DM). In this study, the genotoxic effects of sitagliptin were determined in human lymphocytes by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays. 31.25-1000 μg/mL concentrations of sitagliptin were used. Sitagliptin significantly increased the frequency of CAs and SCEs at the highest concentration at 24 h treatment and all concentrations (except 250 μg/mL for CA, except 31.25 and 62.50 μg/mL for SCE) at 48 h treatment compared with solvent control (DMSO). This compound increased the MN at only the highest concentration compared with the solvent control. Mitotic index (MI) significantly decreased at the three highest concentrations of sitagliptin at 48 h treatment. However, replication (RI) and nuclear division (NDI) indices were not affected at all the treatments. Comet assay results indicated that sitagliptin significantly increased mean comet tail intensity and tail moment at only two concentrations (62.50 and 1000 μg/mL for intensity, 125 and 1000 μg/mL for tail moment), and tail length at all concentrations (except 125 and 500 μg/mL). It was concluded that higher concentration of sitagliptin had genotoxic effects in the human lymphocytes in vitro.
西他列汀是一种用于治疗 2 型糖尿病（T2DM）的抗糖尿病药物的活性成分。在这项研究中，通过染色体畸变（CA）、姐妹染色单体交换（SCE）、微核（MN）和彗星试验，在人淋巴细胞中测定了西他列汀的遗传毒性作用。使用了 31.25-1000μg/mL 的西他列汀浓度。与溶剂对照（DMSO）相比，西他列汀在 24 小时处理时最高浓度和所有浓度（CA 除外的 250μg/mL，SCE 除外的 31.25 和 62.50μg/mL）下显著增加了 CA 和 SCE 的频率。与溶剂对照相比，该化合物仅在最高浓度下增加了 MN。在 48 小时处理时，有三个最高浓度的西他列汀使有丝分裂指数（MI）显著降低。然而，复制（RI）和核分裂（NDI）指数在所有处理中均不受影响。彗星试验结果表明，西他列汀仅在两个浓度（强度为 62.50 和 1000μg/mL，尾部矩为 125 和 1000μg/mL）下显著增加了平均彗星尾强度和尾部矩，并且在所有浓度下（强度为 125 和 500μg/mL 除外）都增加了尾部长度。结论是，较高浓度的西他列汀在体外对人淋巴细胞具有遗传毒性作用。
