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本文报告了三尖杉酯碱对艾氏腹水癌和小鼠L_(1210)白血病细胞DNA 聚合酶α的抑制作用。癌细胞破碎后,经超速离心,DEAE-纤维素和磷酸纤维素P_(11)柱层析部分纯化了DNA 聚合酶α。该酶在1μM 三尖杉酯碱存在时的抑制率为40%左右。在一定的三尖杉酯碱浓度范围内,酶的抑制率随药物浓度的增加而升高。经药物预保温的DNA,模板活性没有变化;而经药物预保温的酶,其活性受到了显著的抑制。当酶量或模板量固定不变时,则过量的模板或过量的酶均能降低药物的抑制率。上述结果初步表明三尖杉酯碱可能是酶的竞争性抑制剂。
Here we report the inhibitory effect of harringtonine on DNA polymerase alpha in Ehrlich ascites carcinoma and mouse L_(1210) leukemia cells. After the cancer cells were disrupted, DNA polymerase alpha was partially purified by ultracentrifugation on DEAE-cellulose and phosphocellulose P_(11) column chromatography. The inhibition rate of this enzyme in the presence of 1 μM harringtonine was about 40%. Within a certain range of harringtonine concentration, the inhibition rate of the enzyme increased with increasing drug concentration. In the DNA pre-incubated with the drug, the activity of the template did not change; however, the activity of the enzyme pre-incubated with the drug was significantly inhibited. When the amount of the enzyme or the amount of the template is fixed, excessive amounts of the template or excessive amount of the enzyme can reduce the inhibition rate of the drug. The above results preliminarily showed that harringtonine may be a competitive inhibitor of the enzyme.