Involvement of intracellular ATP in cytotoxicity of topoisomerase II-targetting antitumor drugs.
Involvement of intracellular ATP in cytotoxicity of topoisomerase II-targetting antitumor drugs.
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细胞内 ATP 参与拓扑异构酶 II 靶向抗肿瘤药物的细胞毒性。
DOI：
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发表时间：
1987
期刊：
影响因子：
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通讯作者：
Leroy
中科院分区：
文献类型：
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作者：
G. Kupfer;A. Bodley;Leroy
在小鼠白血病细胞（L1210）中研究了ATP库对替尼泊苷（VM-26）细胞毒性作用的影响。在存在氧化磷酸化解偶联剂DNP的情况下，用VM-26（10 μ M）处理组织培养物中的L1210细胞。同时处理DNP（1 mM）使细胞存活率增加100-200倍。用DNP预处理或后处理对细胞存活几乎没有影响。其他ATP合成的解偶联剂和抑制剂具有类似于DNP的作用。DNP对VM-26细胞毒作用的干扰也见于另一种拓扑异构酶II靶向药物m-AMSA，而不是拓扑异构酶I靶向药物喜树碱。使用纯化的拓扑异构酶II或培养的哺乳动物细胞的研究表明，DNP对VM-26诱导的可裂解复合物的量几乎没有影响。我们提出，一个ATP需要的过程（ES），随后发生的可切割的复合物的形成涉及的拓扑异构酶II靶向药物的细胞毒性作用。
The effect of the ATP pool on the cytotoxic action of teniposide (VM-26) has been studied in mouse leukemia cells (L1210). L1210 cells in tissue culture were treated with VM-26 (10 microM) in the presence of DNP, an uncoupler of oxidative phosphorylation. The simultaneous treatment of DNP (1 mM) increased cell survival 100-200 fold. Pre- or post-treatment with DNP had little effect on cell survival. Other uncouplers and inhibitors of ATP synthesis had effects similar to DNP. The interference of DNP with the cytotoxic action of VM-26 was also seen with another topoisomerase II-targetting drug, m-AMSA, but not with the topoisomerase I-targetting drug camptothecin. Studies using either purified topoisomerase II or cultured mammalian cells had shown that DNP had little effect on the amount of cleavable complexes induced by VM-26. We propose that an ATP requiring process(es) which occurs subsequent to the formation of the cleavable complexes is involved in the cytotoxic action of topoisomerase II-targetting drugs.