用单分子技术研究抗癌药物顺铂对DNA结构的影响

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.

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

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 flexible,with the persistence length decreased significantly from ～52 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 cisplatin-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.