一氧化氮合成酶对AQ_4N放射增敏作用的影响研究  

Effects of iNOS on radiosensitization of AQ_4N in vitro

作　　者：孔肇路[1] 金一尊[1] Chinje E C Stratford I J 

机构地区：[1]复旦大学放射医学研究所,上海200032 [2]英国曼彻斯特药学院

出　　处：《辐射研究与辐射工艺学报》2006年第3期159-162,共4页Journal of Radiation Research and Radiation Processing

基　　金：国家自然科学基金(30500143);国家863计划(2002AA2Z3104)资助

摘　　要：评价1,4-二-[[2-(二甲氨基-N-氧化物)乙醇]氨基]5,8-双羟基氧化蒽-9,10-二酮((1,4-bis-{[2-(dimethylamino-N-oxide)ethyl]amino}-5,8-dihydroxyanthracene-9,10dione),AQ4N)辐射增敏效果和乏氧选择性,分析一氧化氮合成酶(Induciblenitrogenmonoxidesynthase,iNOS)对AQ4N代谢活化的影响和作用特点。结果显示AQ4N是一种低毒性的化合物,仅在乏氧条件显示较弱的细胞毒性,可以引起肿瘤细胞凋亡。AQ4N对肿瘤细胞尤其是乏氧肿瘤细胞具有良好的辐射增敏作用。同亲本细胞相比,iNOS基因转染的细胞克隆,仅在乏氧条件下显示出对AQ4N化学敏感性的增强和细胞的G2/M期阻滞。提示iNOS仅在乏氧条件下参与AQ4N的代谢活化过程。The study aims to evaluate radiosensitization of AQ4N, a new bioreductive agent, and to clarify the role of iNOS in its metabolism. It seemed that AQ4N was a hypoxia-selective radiosensitizer and mainly caused ceils apotosis, iNOS-gene transfected cells showed G2/M phase block 24 hours after treated with AQ4N under hypoxia. The study showed that iNOS could be a target enzyme taking part in AQ4N bioreduction in anaerobic condition. Further work should be done to clarify the enzymology involved in AQ4N bioactivation to improve the application of AQ4N as a radiosensitizer in clinic.

关 键 词：生物还原 AQ4N 细胞凋亡 p450还原酶 辐射增敏 

分 类 号：R730.53[医药卫生—肿瘤] R730.55[医药卫生—临床医学]