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一氧化氮合成酶对AQ4N放射增敏作用的影响研究
引用本文:孔肇路,金一尊,Chinje E C,Stratford I J.一氧化氮合成酶对AQ4N放射增敏作用的影响研究[J].辐射研究与辐射工艺学报,2006,24(3):159-162.
作者姓名:孔肇路  金一尊  Chinje E C  Stratford I J
作者单位: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,英国,M13 9PL
基金项目:国家自然科学基金;国家科技攻关项目
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(Inducible nitlogen monoxide synthase,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AO4N的代谢活化过程。

关 键 词:生物还原  细胞凋亡  p450还原酶  辐射增敏
收稿时间:2005-12-09
修稿时间:2006-02-13

Effects of iNOS on radiosensitization of AQ4N in vitro
KONG Zhaolu,JIN Yizun,Chinje E C,Stratford I J.Effects of iNOS on radiosensitization of AQ4N in vitro[J].Journal of Radiation Research and Radiation Processing,2006,24(3):159-162.
Authors:KONG Zhaolu  JIN Yizun  Chinje E C  Stratford I J
Affiliation:1 The institute of radiation medicine, Fudan university, Shanghai 200032; 2 .Ontology Lab, the Pharmacy School of Manchest University, UK, M13 9PL
Abstract: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.
Keywords:AQ4N
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