Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: Enhancement of radiosensitivity in human glioblastoma cells by the DNA N-mustard alkylating agent BO-1051 through augmented and sustained DNA damage response. | Chu et al. Radiation Oncology 2011 6 7 http content 6 1 7 RADIATION ONCOLOGY RESEARCH Open Access Enhancement of radiosensitivity in human glioblastoma cells by the DNA N-mustard alkylating agent BO-1051 through augmented and sustained DNA damage response Pei-Ming Chu1 Shih-Hwa Chiou2 3 4t Tsann-Long Su5t Yi-Jang Lee6t Li-Hsin Chen3 Yi-Wei Chen4 7 Sang-Hue Yen7 Ming-Teh Chen8 Ming-Hsiung Chen8 Yang-Hsin Shih8 Pang-Hsien Tu5 Hsin-I Ma1 Abstract Background 1- 4- Bis 2-chloroethyl amino phenyl -3- 2-methyl-5- 4-methylacridin-9-ylamino phenyl urea BO-1051 is an N-mustard DNA alkylating agent reported to exhibit antitumor activity. Here we further investigate the effects of this compound on radiation responses of human gliomas which are notorious for the high resistance to radiotherapy. Methods The clonogenic assay was used to determine the IC50 and radiosensitivity of human glioma cell lines U87MG U251MG and GBM-3 following BO-1051. DNA histogram and propidium iodide-Annexin V staining were used to determine the cell cycle distribution and the apoptosis respectively. DNA damage and repair state were determined by Ỵ-H2AX foci and mitotic catastrophe was measure using nuclear fragmentation. Xenograft tumors were measured with a caliper and the survival rate was determined using Kaplan-Meier method. Results BO-1051 inhibited growth of human gliomas in a dose- and time-dependent manner. Using the dosage at IC50 BO-1051 significantly enhanced radiosensitivity to different extents The sensitizer enhancement ratio was between and at 10 of survival fraction . The radiosensitive G2 M population was raised by BO-1051 whereas apoptosis and mitotic catastrophe were not affected. Ỵ-H2AX foci was greatly increased and sustained by combined BO-1051 and g-rays suggested that DNA damage or repair capacity was impaired during treatment. In vivo studies further demonstrated that BO-1051 enhanced the radiotherapeutic effects on GBM-3-beared xenograft tumors by
