In vitro genotoxic effedts of the active ingredients of antidiabetic drug, metformin

Metformin is an active ingredient of antidiabetic drug which is used in the treatment of Diabetes Mellitus. In this study, the in vitro genotoxic effects of Metformin has been determined in human peripheral blood lymphocytes by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN) and comet assays. In addition, the effects of Metformin on mitotic index (MI), replication index (RI) and nuclear division index (NDI) were also investigated. 12.5; 25.0; 50.0; 75.0; 100.0 and 125.0 µg/mL concentrations of Metformin were used. Metformin significantly increased the frequency of chromosome aberrations (except treatment of Metformin for 24 h) and sister chromatid exchanges compared with the negative control. MN frequency was not effected at any concentrations except 125.0 ?g/mL. Mitotic index was significantly decreased at all treatments but this decrease is not dose dependent. Nuclear division index was reduced at two highest concentrations (100.0 and 125.0 ?g/mL) and no significant effect observed at other concentrations. No difference observed in replication index. According to the comet assay results Metformin did not effect tail moment and tail intensity (except to 125.0 µg/mL) at all concentrations. In contrast, Metformin significantly increased the comet tail length at four concentrations (25.0; 75.0, 100.0 and 125.0 µg/mL). It is concluded that higher concentrations of Metformin have clastogenic and viianeugenic effects especially at long time exposure on human lymphocytes in vitro.