Zhu C, Johansson M, Karlsson A
Division of Clinical Virology, Karolinska Institute, Huddinge University Hospital, S-141 86, Stockholm, Sweden.
FEBS Lett. 2000 Jun 2;474(2-3):129-32. doi: 10.1016/s0014-5793(00)01569-6.
The anti-leukemic nucleoside analogs 1-beta-D-arabinofuranosylcytosine (araC) and 9-beta-D-arabinofuranosylguanine (araG) are dependent on intracellular phosphorylation for pharmacological activity. AraC is efficiently phosphorylated by deoxycytidine kinase (dCK). Although araG is phosphorylated by dCK in vitro, it is a preferred substrate of mitochondrial deoxyguanosine kinase. We have used autoradiography to show that araC was incorporated into nuclear DNA in Molt-4 and CEM T-lymphoblastoid cells as well as in Chinese hamster ovary cells. In contrast, araG was predominantly incorporated into mitochondrial DNA in the investigated cell lines, without detectable incorporation into nuclear DNA. These data suggest that the molecular targets of araG and araC may differ.
抗白血病核苷类似物1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷，araC）和9-β-D-阿拉伯呋喃糖基鸟嘌呤（阿糖鸟苷，araG）的药理活性依赖于细胞内磷酸化。阿糖胞苷可被脱氧胞苷激酶（dCK）有效磷酸化。虽然阿糖鸟苷在体外可被dCK磷酸化，但它是线粒体脱氧鸟苷激酶的优选底物。我们利用放射自显影术表明，阿糖胞苷在Molt-4和CEM T淋巴母细胞样细胞以及中国仓鼠卵巢细胞中被掺入核DNA。相比之下，在所研究的细胞系中，阿糖鸟苷主要被掺入线粒体DNA，而未检测到其掺入核DNA。这些数据表明，阿糖鸟苷和阿糖胞苷的分子靶点可能不同。
