Radio-resistance induced by nitric oxide to heavy ion irradiation in A172 human glioma cells

Radio-resistance induced by nitric oxide to heavy ion irradiation in A172 human glioma cells 1 2 first-author 1 corresp Corresponding author. E-mail: zhangh@impcas.ac.cn Corresponding author. E-mail: zhangh@impcas.ac.cn zhangh@impcas.ac.cn 3 Institute of Modern Physics , Chinese Academy of Sciences , Lanzhou 730000, China; Institute of Modern Physics , Chinese Academy of Sciences , Lanzhou 730000, China; Graduate School of Chinese Academy of Sciences, Beijing 100049, China; Graduate School of Chinese Academy of Sciences, Beijing 100049, China; The First Hospital of Lanzhou University, Lanzhou 730000, China The First Hospital of Lanzhou University, Lanzhou 730000, China To investigate effects of nitric oxide on cellular radio-sensitivity, three human glioma cell lines, i.e. A172, A172 transfected green fluorescence protein (EGFP) gene (EA172) and A172 transfected inducible nitric oxide synthesis (iNOS) gene (iA172), were irradiated by 12 C 6+ ions to 0, 1 or 2Gy. Productions of nitric oxide and glutathione (GSH) in A172, EA172 and iA172 were determined by chemical methods, cell cycle was analyzed by flow cytometry at the 24th hour after irradiation, and survival fraction of the cells was measured by colorimetric MTT assay at the 5th day after irradiation. The results showed that the concentrations of nitric oxide and GSH in iA172 were significantly higher than in A172 and EA172; the G 2 /M stage arrest induced by the 12 C 6+ ion irradiation was observed in A172 and EA172 but not in iA172 at the 24th hour after exposure; and the survival fraction of iA172 was higher than that of EA172 and iA172. Data suggest that the radio-sensitivity of the A172 was reduced after the iNOS gene transfection. The increase of GSH production and the change of cellular signals such as the cell cycle control induced by nitric oxide may be involved in this radio-resistance. Nitric oxide 12 C 6+ heavy ion A172 human glioma cells Radio-resistance References Worthington J , McCarthy H O , Barrett E , et al . J Gene Med , 2004 , 6 ( 6 ): 673 - 680 . J Gene Med Wang Z , Cook T , Alber S , et al . Cancer Res , 2004 , 64 : 1386 - 1395 . Cancer Res Mitchell J B , Wink D A , DeGraff W , et al . Cancer Res , 1993 , 53 : 5845 - 5848 . Cancer Res Matsumoto H , Hayashi S , Hatashita M , et al . Radiat Res , 2001 , 155 : 387 - 396 . Radiat Res Matsumoto H , Hayashi S , Hatashita M , et al . Int J Radiat Biol , 2000 , 76 : 1649 - 1657 . Int J Radiat Biol Matsumoto H , Hayashi S , Jin Z-H , et al . International Congress Series , 2002 , 1236 : 295 - 298 . International Congress Series May P , May E . Oncogene , 1999 , 18 : 7621 - 7636 . Oncogene Taylor W R , DePrimo S E , Agarwal A , et al . Mol Biol Cell , 1999 , 10 : 3607 - 3622 . Mol Biol Cell Zhu Q , Wani MA , El-Mahdy M , et al . J Biol Chem , 2000 , 275 : 11492 - 11497 . J Biol Chem Hemish J , Nakaya N , Mittal V , et al . J Biol Chem , 2003 , 278 : 42321 - 42329 . J Biol Chem Buckley B J , Whorton A R . Am J Physiol Cell Physiol , 2000 , 279 : C1168 - 1176 . Am J Physiol Cell Physiol Shanker G , Aschner M . Mol Brain Res , 2003 , 110 : 85 - 91 . Mol Brain Res Terato H , Ide H . Biol Sci Space , 2004 , 18 : 206 - 215 . Biol Sci Space Zhang M W , Peng X X , Hu P , et al . Acta Pharmacol Sin (in Chinese) , 1998 , 19 : 121 - 127 . Acta Pharmacol Sin (in Chinese) HUANG Qian , XU Ping , LIU Wenwen , et al . Chin J Ophthalmol (in Chinese) , 2001 , 37 ( 4 ): 248 - 251 . Chin J Ophthalmol (in Chinese) 10.1016/S1001-8042(07)60062-1 Q691 Supported by grants from the National Natural Science Foundation of China (10675151) , the Key Scientific Technology Research Projects of Gansu Province (2GS052-A43-00 8-02, 2GS063-A43-012) and the Scientific Technology Research Project of Lanzhou-Chinese Academy of Sciences (06-2-58) . 2007-04-11 2007-10-20 2021-01-19 2007 Nuclear Science and Techniques 05 18