甲基苯丙氨酸氮芥(AT_(1420))对艾氏腹水癌细胞的杀伤动力学及对HeLa细胞DNA合成的抑制

THE EFFECTS OF METHYLMERPHALAN(AT-1420) ON THE CYTOKINETICS OF EHRLICH ASCITIC TUMOR CELLS AND ON THE DNA SYNTHESIS OF HeLa CELLS

本实验室以前的工作表明AT_(1420)具有显著抗瘤活性而无蓄积毒性。本文进一步表明:AT_(1420)主要抑制指数生长期的EAC细胞;在体外对培养中的HeLa细胞有直接细胞毒作用,100μg/ml浓度对~3H-TdR参入的抑制率43—55％.50μg/ml抑制率23—26％,25μg/ml抑制率为16％。采用显微分光光度计测定单个细胞DNA含量,并用电脑分析数据,对EAC细胞增殖周期动力学研究表明:用药后4小时即出现G_1期细胞堆积,进入S期受阻。用药后24小时仍有大量细胞堆积于G_1期,并出现相当部分低DNA含量的细胞。提示临床应用AT_(1420)时不宜与S期特异性药物(如MTX AraC等)同时使用以免产生自限作用而降低疗效。

In our previous studies it was proved that Methylmerphalan (AT-1420) possessed significant antitumor activity against some kinds of transplantable tumors in mice without accumulating toxicity. In this paper it was further shown that AT-1420 strongly inhibited EAC cells in logarithmic growth phase- Direct cytotoxicity was found in cultivated HeLa cells. The 3 H-TdR incorporation into HeLa cells was inhibited by 43-66% under the conce-tration of 10μg/ml of AT-1420, by 23- 26% under 50 μ g/ml. In the cytokinetic studies using computerized microspectrophotometer it was shown that EAC cells accumulated in G 1 phase and was retarded entering into S phase 4 hours after administration of AT-1420. . Many G 1 phase cells and considerable part of the cells with low DNA content were found until 24 hours after administration of AT-1420. It was suggested that AT-1420 is not suitable for use with S Phase specific agents (MTX, AraC and etc) simultaneously, in order to avoid the lowering of therapeutic effect caused by self_limiting effect.