Development of chemotherapy according to induction of DNA Topoisomerase activity.

1996 Fiscal Year Final Research Report Summary

• Project/Area Number: 07671325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Saitama Medical School
• Principal Investigator: ANZAI Haruyuki SAITAMA MEDICAL SCHOOL,FIRST DEPARTMENT OF SURGERY,ASSISTANT PROFESSOR, 医学部, 講師 (30193098)
• Project Period (FY): 1995 – 1996
• Keywords: DNA TOPOISOMERASE / TOPOTECAN / ETOPOSIDE

Research Abstract

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.