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 50μM for 2h and irradiated with 6MV 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 24h. It was found that pretreatment with metformin (10 and 50μM) increased the percentage of cell viability. A highly significant dose modifying factor (DMF) 1.35 and 1.42 was observed for 10 and 50μM metformin, respectively. Metformin (10 and 50μM) 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 50μM) 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 50μM) 2h 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.
Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences and Health Services, Tehran, Iran.
Mohsen
M
Cheki
Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences and Health Services, Tehran, Iran. Electronic address: shirazia@sina.tums.ac.ir.
Alireza
A
Shirazi
Department of Biosciences and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran.
Aziz
A
Mahmoudzadeh
Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences and Health Services, Tehran, Iran.
Javad Tavakkoly
JT
Bazzaz
Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Seyed Jalal
SJ
Hosseinimehr
D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects* / Q000528:radiation effects; D019610:Cytoprotection / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D011835:Radiation Protection; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D011837:Radiation-Protective Agents; D008687:Metformin
Cytotoxicity; Genotoxicity; Human blood lymphocytes; Ionizing radiation; Metformin