STUDIES OF TOPOISOMERASE II AS TARGET OF ACTION OF ANTICANCER DRUG

从小鼠L1210中提纯DNA拓扑异构酶II和I 和中国仓鼠(DC3F；DC3F/9-OHE)细胞。提纯程序 是基于其DNA连接和拓扑异构酶II的检测 在m-AMSA存在下的断裂活性。纯化的拓扑异构酶II 在相同的情况下产生与蛋白质相关的DNA断裂 在细胞中产生与蛋白质相关的DNA断裂的化合物。在……里面 此外，在这两种情况下，断裂都不允许DNA旋转，他们的 5‘-末端与酶共价连接，它们的形成可以是 被高浓度的2-甲基-9-羟基椭圆形所抑制。它是 因此，拓扑异构酶II很可能是 M-AMSA、蒽环类、椭圆形和表鬼臼毒素，由 在这中间，它们会产生与蛋白质相关的DNA断裂。 氰吗啉阿霉素与DNA具有独特的相互作用模式 涉及DNA链间交联和无(或弱)抗拓扑异构酶II 活动。M-AMSA似乎通过与拓扑异构酶II直接相互作用 它的侧链的中间体。DNA嵌入不足以 影响拓扑异构酶II。例如，9-氨基吖啶是较好的 嵌入剂优于m-AMSA，但不含(或弱于)抗拓扑异构酶II 活动。多胺影响拓扑异构酶活性，并可能起到 在哺乳动物细胞中控制DNA拓扑异构酶的作用。

DNA topoisomerase II and I can be purified to homogeneity from mouse L1210 and Chinese hamster (DC3F; DC3F/9-OHE) cells. The purification procedure is based upon the detection of topoisomerase II by its DNA linking and breaking activity in the presence of m-AMSA. Purified topoisomerase II produced protein-associated DNA breaks in the presence of the same compounds that produce protein-associated DNA breaks in cells. In addition, in both cases the breaks do not allow DNA swivelling, their 5'-termini are covalently linked to the enzyme and their formation can be inhibited by high concentrations of 2-methyl-9-hydroxyellipticinium. It is therefore likely that topoisomerase II is the intracellular target of m-AMSA, anthracyclines, ellipticines and epipodophyllotoxins, by the intermediate of which they produce the protein-associated DNA breaks. Cyanomorpholinoadriamycin has a unique mode of interaction with DNA involving DNA interstrand crosslinks and no (or weak) antitopoisomerase II activity. m-AMSA seems to interact directly with topoisomerase II by the intermediate of its side chain. DNA intercalation is not sufficient to affect topoisomerase II. For example, 9-aminoacridine is a better intercalator than m-AMSA but has no (or weak) antitopoisomerase II activity. Polyamines affect topoisomerases activities and could play a role in controlling DNA topoisomerases in mammalian cells.