叠氮胸苷对人胶质瘤细胞辐射后DNA损伤单链修复的影响  

Effect of Azidothymidine on irradiation-induced DNA single strand damage and repair of human glioma cell lines

作　　者：於海军[1] 骆志国[1] 戴静[1] 周福祥[1] 谢丛华[1] 周云峰[1] 

机构地区：[1]武汉大学中南医院肿瘤放化疗科,湖北武汉430071

出　　处：《肿瘤防治杂志》2005年第20期1525-1529,共5页China Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金资助项目(30171063);湖北省自然科学基金资助项目(2004ABA165)

摘　　要：目的:观察逆转录酶抑制剂叠氮胸苷(AZT,3'-azido-3'-deoxythmidine)对人脑胶质瘤细胞U251放射性DNA单链损伤(singlestrand break,SSB)修复的影响,探讨其放射增敏的机制。方法:实验分为四组:1)空白组:未行AZT与γ射线处理;2)放射组:细胞接受2Gyγ射线单次照射;3)加药组:细胞培养液中加入终浓度为0·8mmol/L的AZT作用24h;4)药放组:细胞经过0·8mmol/L的AZT作用24h后再行2Gyγ射线单次照射。用碱性单细胞凝胶电泳方法检测辐射后DNA SSB的尾矩。结果:空白组与加药组细胞无慧尾,两组差异无统计学意义,F=0·238,P=0·628,表明AZT本身不会导致DNASSB;而放射组和药放组均出现明显的彗星图象,药放组与放射组的初始SSB相比差异无统计学意义,P=0·628,但前者的修复速度较慢(15min、30min、1h和2h时间点两组的SSB差异有统计学意义,F值分别为4·652、4·160、7·134和4·715,P值分别为0·038、0·049、0·011和0·037),照射后2h放射组的SSB基本修复完全(放射组与空白组比较,P=0·099),而药放组仍有显著残留(药放组与空白组比较,P<0·0001)。结论:端粒酶抑制剂AZT放射增敏可能与其抑制DNASSB的修复有关。肿瘤防治杂志,2005,12(20)OBJECTIVE： To study radiosensitization of reverse transcriptase inhibitor （ 3＇-azido-3 ＇-deoxythmidine, AZT）, we investigate the effects of AZT combined with 7-irradiation on DNA single strand breaks induced by irradiation in human malignant glioma cells U251. METHODS： Exponentially growing U251 cells were divided into four groups： 1） control;2） to be treated with irradiation （2 Gy）;3） to be treated with 0.8 mm/L AZT for 24 h： 4） to be treated with AZT and irradiation both. DNA dam age induced by irradiation was determined by alkaline single cell gel electrophoresis assay （comet assay）. The tail moment was used to quantitate the primary DNA damage and subsequent repair ability. RESULTS： Immediately after irradiation, the type comet image was observed in groups 2 and 4 but not in groups 1 and 3. There was no significantly difference in the level of initial SSB between group 2 and group 4 （F=0.238,P=0.628）. While the rates of repair of SSB was slower in group 4 than that in group 2 （RT vs AZT＋RT at the time 15min,30min,1 h,2 h after irradiation, F=4. 652,P=0.038,F=4. 160,P =0.049, F=7. 134,P=0.011, F=4.715,P=0.037 respectively）. The irradiation in duced DNA SSB was rather efficiently repaired in group 2 within 2 h （RT vs Control, P=0. 099）, while there was still significant residual SSB in group 4 at that time （AZT＋RT vs Control, P〈0. 000 1 ）. CONCLUSION ： The mechanism of radiosensitization of telomerase inhibitor AZT may be related with the inhibition of the repair of DNA single strand break （DNA SSB）.

关 键 词：神经胶质瘤 叠氯化合物 DNA损伤 胸苷 辐射耐受性 

分 类 号：R739.4[医药卫生—肿瘤]