非嵌合性抗癌药物对小牛胸腺DNA拓扑异构酶Ⅰ活力的影响

EFFECT OF SOME NONINTERCALATIVE ANTITUMOR DRUGS ON THE ACTIVITY OF CALF THYMUS DNA TOPOISOMERASE Ⅰ

本文介绍从小牛胸腺中分离纯化DNA拓扑异构酶Ⅰ(简称拓扑酶Ⅰ)的方法,并用于检测了几种非嵌合性抗癌药物对该酶活力的影响。实验结果表明,一些已知的抗癌药物确有抑制DNA拓扑酶Ⅰ的作用。以抑制DNA拓扑酶Ⅰ为检测指标的方法可为筛选抗癌药物提供新的手段,并为药物抗癌机制的研究开辟了新的途径。

DNA topoisomerase Ⅰ has been isolated from the nuclei of calf thymus by PEG fractionation and chromatography on P11 and on Bio-Rex 70. Either a positive or negative suPercoiled pBR322 DNA can be relaxed by the enzyme. The activity of Topo Ⅰ is Mg^(2+) and ATP independent. Some of nonintercalative antitumor drugs such as camptothecine, hydroxycamptothecine, cyclophosphamide, methotrexate and mitomycin C were found to inhibitthe activity of Tdpo Ⅰ. The results suggest that DNA Topo Ⅰ can be used to screen new nonintercalative antitumor drugs as a target protein.