Pessina A
Institute of Medical Microbiology, University of Milan, Italy.
Cytotechnology. 1993;12(1-3):127-35. doi: 10.1007/BF00744661.
Topoisomerase I is a nuclear enzyme able to catalyse the relaxation of supercoiled DNA by introducing single-stranded breaks in DNA molecule. Its function seems important to prepare DNA for many processes such as recombination, DNA repair and RNA transcription. The most important drugs active as inhibitors of topoisomerase I are represented by camptothecin and its derivatives which were developed as promising anticancer drugs. Since selectivity of action is essential for an antitumor drug, many studies were performed to investigate the mechanisms by which cancer cells become resistant to drug treatment by developing a condition of multiple drug resistance (MDR). This article analyses the role of topoisomerase I in cell functions, considers the cellular effects of topo I poisons and discusses the ways by which tumoral cells may become resistant to these drugs with a special attention to MDR mechanisms.
拓扑异构酶I是一种核酶，能够通过在DNA分子中引入单链断裂来催化超螺旋DNA的松弛。其功能对于为许多过程（如重组、DNA修复和RNA转录）准备DNA似乎很重要。作为拓扑异构酶I抑制剂具有活性的最重要药物以喜树碱及其衍生物为代表，它们被开发为有前景的抗癌药物。由于作用的选择性对于抗肿瘤药物至关重要，因此进行了许多研究来调查癌细胞通过产生多药耐药（MDR）状态而对药物治疗产生耐药性的机制。本文分析了拓扑异构酶I在细胞功能中的作用，考虑了拓扑异构酶I毒物的细胞效应，并讨论了肿瘤细胞可能对这些药物产生耐药性的方式，特别关注MDR机制。
