Division of Hematology-Oncology, The Barbara Ann Karmanos Cancer Institute, Wayne State University, 3900 John R., Detroit, MI, U.S.A.
Cytotechnology. 1998 Sep;27(1-3):149-64. doi: 10.1023/A:1008008719699.
DNA topoisomerase I is a nuclear enzyme which catalyzes the conversion of the DNA topology by introducing single-strand breaks into the DNA molecule. This enzyme represents a novel and distinct molecule target for cancer therapy by antitopoisomerase drugs belonging to the campthotecin series of antineoplastics. As many tumors can acquire resistance to drug treatment and become refractary to the chemotherapy it is very important to investigate the mechanisms involved in such a drug resistance for circumventing the phenomenon. This article describes the role of topoisomerase I in cell functions and the methods used to assess its in vitro catalytic activity. It reviews the mechanisms of cytotoxicity of the most specific antitopoisomerase I drugs by considering also the phenomenon of drug resistance. Some factors useful to drive the future perspectives in the development of new topoisomerase I inhibitors are also evidenced and discussed.
DNA 拓扑异构酶 I 是一种核酶，通过在 DNA 分子中引入单链断裂来催化 DNA 拓扑结构的转换。该酶代表了一种新型的、独特的分子靶点，通过属于喜树碱类抗肿瘤药物的抗拓扑异构酶药物进行癌症治疗。由于许多肿瘤可以对药物治疗产生耐药性，并对化疗产生抗药性，因此研究这种耐药性涉及的机制以避免这种现象非常重要。本文描述了拓扑异构酶 I 在细胞功能中的作用，以及用于评估其体外催化活性的方法。它还考虑了耐药性现象，综述了最特异的抗拓扑异构酶 I 药物的细胞毒性机制。还提出和讨论了一些有助于推动新型拓扑异构酶 I 抑制剂开发的未来展望的因素。
