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《ACTA PHARMACEUTICA SINICA》 1999-01
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EFFECT OF HOWIINOL(GHM 10) ON THE STRUCTURE OF DNA MOLECULES AND ACTIVITY OF DNA TOPOISOMERASE II IN L1210 CELLS

He Jianhua(He JH) and Xu Chengxiong(Xu CX) (Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050)  
AIM: To study the mechanism of inhibitory action of howiinol A(GHM 10) on synthesis of DNA in cancer cells. METHODS: Single cell gel electrophoresis was used to detect the DNA molecular damage induced by GHM 10 in L1210 cells. Alkaline elution technique was used to investigate the effect of GHM 10 on the length of DNA strands of L1210 cells. Dehelix effect of GHM 10 on superhelix pUC 18 DNA was used to estimate its influence on the activity of DNA topoisomerase II. RESULTS: After L1210 cells were treated with 4 and 10 μg·ml -1 of GHM 10 for 4 5 h, comet like tails could be seen in cells under a fluorescence microscope after electrophoresis, indicating that DNA damage was induced by GHM 10. DNA single strand breaks were demonstrated when L1210 cells were treated with GHM 10 in concentrations of 4 and 25 μg·ml -1 for 5 h. When L1210 cells or protein isolated from L1210 cells were treated with GHM 10, the activity of DNA topoisomerase II was inhibited. CONCLUSION: GHM 10 induces damage to DNA molecules in L1210 cells and inhibits the activity of topoisomerase II both inside and outside the cells.
【CateGory Index】: R963
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