The radioprotective effect of metformin against cytotoxicity and genotoxicity induced by ionizing radiation in cultured human blood lymphocytes

Metformin is a widely prescribed drug used in the treatment of patients with type 2 diabetes. In this study, the radioprotective effect of metformin was investigated against cytotoxicity and genotoxicity induced by ionizing radiation (IR) in human peripheral blood lymphocytes. Human lymphocytes were treated with metformin at concentrations 10 and 50 mu M for 2 h and irradiated with 6 MV X-rays. The radiation antagonistic potential of metformin was assessed by MTT[3-(4,5-dimethyl-2-thiaozolyl)-2,5-diphenyl-2H tetrazolium bromide] assay, chromosomal aberration (CA) analysis, cytokinesis blocked micronucleus (CBMN) assay, and flow cytometry. Observations demonstrated a radiation-dose-dependent decrease in the percentage of cell viability after 24 h. It was found that pretreatment with metformin (10 and 50 mu M) increased the percentage of cell viability. A highly significant dose modifying factor (DMF) 1.35 and 1.42 was observed for 10 and 50 mu M metformin, respectively. Metformin (10 and 50 mu M) pretreatment significantly decreased the frequency of dicentrics (DCs), acentric fragments (AFs), rings (RIs), micronuclei (MN), and nucleoplasmic bridges (NPBs) in irradiated human peripheral blood lymphocytes. Also, treatment with metformin (10 and 50 mu M) without irradiation did not increase the number of MN, NPBs, DCs, AFs, RIs, and did not show a cytostatic effect in the human peripheral blood lymphocytes. On the other hand, metformin treatment (10 and 50 mu M) 2 h prior to irradiation significantly reduced X-radiation induced apoptotic incidence in human lymphocytes. The present study demonstrates metformin to be an effective radioprotector against DNA damage and apoptosis induced by IR in human lymphocytes. These data have an important application for the protection of lymphocytes from the genetic damage and side-effects induced by radiotherapy in cancer patients. (C) 2016 Elsevier B.V. All rights reserved.