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

被引：61
作者：
Cheki, Mohsen [1 ]
Shirazi, Alireza [1 ]
Mahmoudzadeh, Aziz [2 ]
Bazzaz, Javad Tavakkoly [3 ]
Hosseinimehr, Seyed Jalal [4 ]
机构：
[1] Tehran Univ Med Sci & Hlth Serv, Dept Med Phys & Biomed Engn, Fac Med, Keshavarz Blvd,Poursina Ave, Tehran, Iran
[2] Malek Ashtar Univ Technol, Dept Biosci & Biotechnol, Tehran, Iran
[3] Tehran Univ Med Sci & Hlth Serv, Dept Med Genet, Fac Med, Tehran, Iran
[4] Mazandaran Univ Med Sci, Dept Radiopharm, Pharmaceut Sci Res Ctr, Fac Pharm, Sari, Iran
来源：
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS | 2016年 / 809卷
关键词：
Ionizing radiation; Metformin; Cytotoxicity; Genotoxicity; Human blood lymphocytes; INDUCED APOPTOSIS; DNA-DAMAGE; OXIDATIVE DAMAGE; IN-VITRO; ANTIOXIDANT; PROTECTS; IRRADIATION; MODULATION; CELLS; P53;
D O I：
10.1016/j.mrgentox.2016.09.001
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
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.
引用
收藏
页码：24 / 32
页数：9
相关论文
共 61 条
[1]   Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice [J].
Aleisa, A. M. ;
Al-Rejaie, S. S. ;
Bakheet, S. A. ;
Al-Bekari, A. M. ;
Al-Shabanah, O. A. ;
Al-Majed, Abdulhakeem ;
Al-Yahya, Abdulaziz A. ;
Qureshi, S. .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2007, 634 (1-2) :93-100
[2]   Metformin Reduces Endogenous Reactive Oxygen Species and Associated DNA Damage [J].
Algire, Carolyn ;
Moiseeva, Olga ;
Deschenes-Simard, Xavier ;
Amrein, Lilian ;
Petruccelli, Luca ;
Birman, Elena ;
Viollet, Benoit ;
Ferbeyre, Gerardo ;
Pollak, Michael N. .
CANCER PREVENTION RESEARCH, 2012, 5 (04) :536-543
[3]   Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells [J].
Amador, Rubem R. ;
Figueiro Longo, Joao Paulo ;
Lacava, Zulmira G. ;
Dorea, Jose G. ;
Almeida Santos, Maria de Fatima M. .
GENETICS AND MOLECULAR BIOLOGY, 2012, 35 (01) :153-158
[4]   Metformin protects against doxorubicin-induced cardiotoxicity: Involvement of the adiponectin cardiac system [J].
Asensio-Lopez, Mari C. ;
Lax, Antonio ;
Pascual-Figal, Domingo A. ;
Valdes, Mariano ;
Sanchez-Mas, Jesus .
FREE RADICAL BIOLOGY AND MEDICINE, 2011, 51 (10) :1861-1871
[5]   Assessment of genomic instability in normal and diabetic rats treated with metformin [J].
Attia, S. M. ;
Helal, G. K. ;
Alhaider, A. A. .
CHEMICO-BIOLOGICAL INTERACTIONS, 2009, 180 (02) :296-304
[6]  
Begum N., 2012, Biomed Prev Nutr, V2, P16, DOI [10.1016/j.bionut.2011.11.003, DOI 10.1016/J.BIONUT.2011.11.003]
[7]   Apigenin ameliorates gamma radiation-induced cytogenetic alterations in cultured human blood lymphocytes [J].
Begum, Naziya ;
Prasad, N. Rajendra ;
Kanimozhi, G. ;
Hasan, Annie Q. .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2012, 747 (01) :71-76
[8]   An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress [J].
Bonnefont-Rousselot, D ;
Raji, B ;
Walrand, S ;
Gardès-Albert, M ;
Jore, D ;
Legrand, A ;
Peynet, J ;
Vasson, MP .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2003, 52 (05) :586-589
[9]   Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients [J].
Chakraborty, Arpita ;
Chowdhury, Subhankar ;
Bhattacharyya, Maitree .
DIABETES RESEARCH AND CLINICAL PRACTICE, 2011, 93 (01) :56-62
[10]   Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage [J].
Chen, Liming ;
Liu, Yinghui ;
Dong, Liangliang ;
Chu, Xiaoxia .
CELL STRESS & CHAPERONES, 2015, 20 (02) :289-295
1234567