Staub M, Sasvári-Székely M, Spasokukockaja T, Antoni F
Mol Cell Biochem. 1982 Jan 16;42(1):37-44. doi: 10.1007/BF00223537.
The effect of arabinosyl cytosine (ara-C) was studied on the uptake, phosphorylation and incorporation of 3H-thymidine in human tonsillar lymphocyte cultures is described along with its effect on the level of DNA polymerase and thymidine Kinase activities induced by phytohaemagglutinin (PHA). Freshly isolated tonsillar lymphocytes are stimulated cells with a remarkably high activity of DNA polymerase alpha and thymidine kinase. During in vitro culture, these stimulated cells are transformed to the resting state with low DNA polymerase and thymidine kinase activity. However, a new DNA synthesising cycle can be induced by PHA with maximum at 48 h. 10(-6) M ara-C inhibited the incorporation of 3H-thymidine by 90-95%. This inhibition may be reversed by rinsing the cells. The inhibition of the transport of 3H-thymidine seems to be only a consequence of the inhibitory effect of ara-C on the DNA polymerisation reaction, because at 10 degrees C, where DNA synthesis was arrested, ara-C does not influence the uptake and the phosphorylation of 3H-thymidine. Ara-C (10(-6) M) abolished also the PHA induced elevation of DNA polymerase alpha and thymidine kinase activities without influencing protein synthesis of the cell. This supports a coordinated regulation mechanism between DNA synthesis and the synthesis of enzymes involved in DNA replication.
本文描述了阿糖胞苷（ara-C）对人扁桃体淋巴细胞培养物中3H-胸腺嘧啶核苷摄取、磷酸化和掺入的影响，以及它对植物血凝素（PHA）诱导的DNA聚合酶和胸苷激酶活性水平的影响。新鲜分离的扁桃体淋巴细胞是具有显著高活性DNA聚合酶α和胸苷激酶的刺激细胞。在体外培养过程中，这些刺激细胞转变为具有低DNA聚合酶和胸苷激酶活性的静止状态。然而，PHA可诱导新的DNA合成周期，在48小时达到最大值。10(-6)M的ara-C可抑制90-95%的3H-胸腺嘧啶核苷掺入。这种抑制作用可通过冲洗细胞来逆转。3H-胸腺嘧啶核苷转运的抑制似乎只是ara-C对DNA聚合反应抑制作用的结果，因为在10℃时，DNA合成停止，ara-C不影响3H-胸腺嘧啶核苷的摄取和磷酸化。ara-C（10(-6)M）也消除了PHA诱导的DNA聚合酶α和胸苷激酶活性的升高，而不影响细胞的蛋白质合成。这支持了DNA合成与参与DNA复制的酶合成之间的协调调节机制。
