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^(125)I-UdR对C6胶质瘤细胞DNA靶点放疗作用的实验研究 被引量:1

Experimental study of DNA-targeting radiotherapy by using ^( 125) I-UdR to treat C6 glioma
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摘要 目的 探讨 5 1 2 5I 2′ 脱氧尿苷 (1 2 5I UdR)对C6胶质瘤细胞DNA靶点放疗作用及其作用机制。方法 体外培养C6胶质瘤细胞 ,行克隆形成和生长抑制分析 ,并建立C6 Wistar脑胶质瘤模型 ,实验组、对照组和空白组分别于肿瘤局部注射1 2 5I UdR、1 2 7I UdR和生理盐水 ,5d后处死动物 ,测量肿瘤质量和直径 ,行流式细胞仪分析、增殖细胞核抗原 (PCNA)免疫组织化学染色和大鼠生存分析。结果 1 2 5I UdR各实验组生长曲线抑制 ,克隆形成、肿瘤大小和质量较对照组和空白组明显降低 ;PCNA指数、增殖指数、肿瘤S期细胞比例明显降低 ;凋亡指数增高。1 2 5I UdR实验组较对照及空白组生存时间延长。结论 1 2 5I UdR可抑制C6胶质瘤细胞增殖 ,诱导凋亡 ,具有进一步临床应用的前景和价值。 Objective To investigate the action and mechanism of 5 125 I 2′ deoxyuridine ( 125 I UdR) in DNA targeting radiotherapy of C6 glioma in a rat model. Methods After cultivating C6 glioma cells, we analyzed the growth suppression and clonogenic formation and established a C6/Wistar glioma model. 125 I UdR, 127 I UdR or 0.9% saline was injected separately into the tumors of experimental group, control group or sham group, respectively. The fresh tumor tissues of three groups were taken 5 d later for flow cytometric analysis, proliferation cell nuclear antigen (PCNA) immunohistochemistry and measurement of the diameter and weight of the tumors; and animal survival in 50 d was followed. Results The cell growth cycle in experimental group was suppressed. Clonogenic formation, tumor diameter and weight were lower in experimental group than in control and sham group; PCNA index, proliferation index and S phase cell fraction decreased, apoptosis index increased. The median survival of the animals treated with 125 I UdR was twice longer than that of control animals treated with 127 I UdR or saline. All results of the indexes of the experimental group were statistically different from that of the other two groups ( P <0.05). Conclusions 125 I UdR is a cell cycle dependent agent, it can selectively kill tumor cells in S phase, significantly suppress the proliferation of C6 glioma cell, trigger apoptosis, and extend the survival of tumor bearing rats. On the whole, 125 I UdR possesses a great value and good prospect in clinical application.
出处 《中华核医学杂志》 CAS CSCD 北大核心 2003年第3期145-147,T002,共4页 Chinese Journal of Nuclear Medicine
基金 四川省卫生厅科研基金资助项目 (981 0 51 )
关键词 脑胶质瘤 放射疗法 ^125I—UdR DNA靶点 实验研究 体外培养 增殖细胞核抗原 免疫组织化学 Glioma Tumor cells, cultured Radiotherapy Deoxyuridine Iodine radioisotopes Rats
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参考文献8

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同被引文献13

  • 1金问森,季其仁,姚涌病,徐师国,徐生新,肖林林.5-^(125)I-2′脱氧尿嘧啶核苷杀伤大鼠C_6细胞的实验研究[J].安徽医科大学学报,2005,40(1):30-33. 被引量:1
  • 2Semanani ES, Wang K, Adelstein SJ, et al. 5-^123I/^125I-iodo-2'- deoxyuridine in metastatic lung cancer: radianpharmaceutical formulation affects targeting. J Nucl Med, 2005,46: 800-806.
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  • 7Dupertuis YM, Xiao WH, De Tribolet N, et al. Unlabelled iododeoxyuridine increases the rate of uptake of ^125I iododeoxyuridine in human xenografted glioblastomas. Eur J Nucl Med Mol Imaging, 2002, 29: 499-505.
  • 8Xiao WH, Dupertuis YM, Mermillod B, et al. Unlabelled iododeoxyuridine increases the cytotoxicity and incorporation of ^125I-iododeoxyuridine in two human glioblastoma cell lines. Nucl Med Commun, 2000, 21 : 9479-9453.
  • 9Dupertuis YM, Buehegger F, Piehard C. A balanced deoxyribonueleo- side mixture increased the rate of DNA incorporation of 5-^125I-iodo-2'- deoxyuridine in glioblastoma cells. Cancer Biother Radiopharm, 2003,18: 7-16.
  • 10Marray RK, Granner DK, Mayes PA, et al. 嘌呤嘧啶核苷酸代谢.宋慧萍,译.哈珀生物化学.北京:科学出版社,2003:348-362.

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