用单分子技术研究抗癌药物顺铂对DNA结构的影响  

Effects of the anticancer drug cisplatin on DNA structure studied by single-molecule methods

作　　者：侯锡苗[1] 张兴华[1] 魏孔吉[1] 季超[1] 窦硕星[1] 王渭池[1] 李明[1] 王鹏业[1] 

机构地区：[1]中国科学院物理研究所软物质物理实验室北京凝聚态物理国家实验室,北京100190

出　　处：《物理》2010年第2期108-112,共5页Physics

基　　金：国家自然科学基金(批准号:10834014;10674173);国家重点基础研究发展计划(批准号:2009CB930704)资助项目

摘　　要：文章作者用磁镊与原子力显微镜研究了抗癌药物顺铂对单个DNA分子结构的影响.当顺铂浓度较低时,DNA链变得柔软,驻留长度从～52 nm显著缩短到～15 nm;当顺铂浓度较高时,DNA表现出凝聚现象.基于单分子拉伸和原子力显微镜(AFM)成像两方面的实验结果,文章作者提出一个顺铂导致的DNA变软(softening)-成环(looping)-缩短(shortening)-凝聚(condensing)模型(简写为SLSC模型)来解释观察到的DNA凝聚,并认为通过远程交联使DNA形成小环结构是铂类抗癌药物作用的重要特征.The structural properties of single DNA molecules treated with the anticancer drug cisplatin were studied with magnetic tweezers and atomic force microscopy （AFM）. Under the effect of low-concentration cisplatin （tens of μM）, the DNA became more flexibie, with the persistence length decreased significantly from 452 to - 15 nm. At a high drug concentration （hundreds of μM）, a DNA condensation phenomenon was observed. Based on the experimental results from both single-molecule and AFM studies, we propose a eisplatin-induced DNA softening-looping-shortening-condensing model to explain this kind of DNA condensation. We think the observed micro-loop structure formation of DNA due to distant crosslinks may be an important feature of the effect of platinum anticancer drugs.

关 键 词：抗癌药物 顺铂 DNA 磁镊 原子力显微镜 单分子 

分 类 号：R96[医药卫生—药理学]