Development of chemotherapy according to induction of DNA Topoisomerase activity.

拓扑异构酶（Topo） I和Topo II对各细胞系的活性与Topo I和Topo II抑制剂的ED50有关。细胞系表明。高活性Topo对Topo抑制剂作为该酶的靶标非常敏感。与同时给药相比，顺序给药Topo I和II抑制剂显示出更强的协同效应。此外，先前给药ED10 Topo抑制剂可协同增加互补Topo抑制剂的杀细胞作用。特别是在Topo I抑制剂预先暴露的细胞株中，Topo I活性较高。研究了Topo I和Topo II抑制剂对Topo酶活性的诱导作用。但在ED10、50 Topo抑制剂暴露后2、4、8、12、24小时，Topo酶活性均未见明显变化。体内条件下，Topo酶活性诱导的最佳剂量和方案也未找到。因此，虽然无法检测到Topo酶活性的诱导，但我们得出结论，在结肠癌化疗的临床应用中，测量Topo I和Topo II酶活性，随后给予Topo抑制剂以对抗较高Topo活性的癌细胞，以及预先给予Topo抑制剂以对抗弱酶活性，必须是重要的。

Topoisomerase (Topo) I and II activities against each cell line were related to ED50 of Topo I and II inhibitor. The cell line which indicated. high activity of Topo is very sensitive to Topo inhibitor as the target of this enzyme.Sequential administration of Topo I and II inhibitor revealed more synergistic effect compared to simultaneous administration of these inhibitor. In addition, the precedent administration of ED10 Topo inhibitor increase the cytocidal effect of complementary Topo inhibitor synergistically. Especially, this phenomenon was observed in the cell line which showed high activity of Topo I when Topo I inhibitor were exposed precedentally.The induction of Topo enzyme activity were studied due to Topo I and II inhibitor. But this phenomenon could not observed although Topo enzyme activity at 2,4,8,12,24 hr after the exposure of ED10,50 Topo inhibitor were measured.Optimal dose and schedule for the induction of Topo enzyme activity could not find out in vivo condition, neither.Therefore, although induction of Topo enzyme activity could not detected we concluded that measurement of Topo I and II enzyme activity, and following administration of Topo inhibitor against higher Topo activity of the cancer cell and precedent administration of Topo inhibitor against weak enzyme activity must be important in the clinical apply for the colon cancer chemotherapy.