Müller W E, Rohde H J, Beyer R, Maidhof A, Lachmann M, Taschner H, Kahn R K
Cancer Res. 1975 Aug;35(8):2160-8.
The influence of 9-beta-D-arabinofuranosyladenine (ara-A) and its 5'-triphosphate derivative on programmed synthesis was tested with an intact cell system as well as with isolated enzyme systems. The effect of ara-A was tested in mouse lymphoma cells (L5178Y). The compound reduces cell proliferation in low concentration by cytostasis; under high ara-A concentration of radioactive precursors into DNA, RNA, and protein showed that ara-A selectively inhibits DNA synthesis. Formation of a polysome complex is not affected by ara-A. [3H]ara-A is incorporated into DNA in an intact cell system; 1 molecule of ara-A is incorporated per 8000 molecules of deoxyadenosine. Most of the ara-A molecules appeared to be in internucleotide linkages. Incorporation of ara-A into RNA could not be detected. 9-BETA-D-Arabinofuranosyladenine 5'-triphosphate (ara-ATP) does not reduce the incorporation rate of the following enzymes, isolated from quail oviducts: DNA-dependent RNA polymerases I and II, polyadenylic acid polymerase, and poly(adenosine diphosphate ribose) polymerase. The compound was found to inhibit DNA synthesis catalyzed by DNA polymerases isolated from quail oviducts and from oncogenic RNA viruses (Rous sarcoma viruses). All the enzymes tested were inhibited by ara-ATP in a competitive way with respect to deoxyadenosine 5'-triphosphate. The highest affinity of ara-ATP, i.e., the highest inhibitory potency of the drug, was found in the assays with the eukaryotic low-molecular DNA-dependent DNA polymerase. The influence on the eukaryotic high-molecular DNA-dependent Dna polymerase was a litte less. Compared to the eukaryotic DNA polymerases, the viral enzymes (RNA-directed DNA polymerase and DNA-directed DNA polymerase) are affected to a smaller extent by ara-ATP. No effects of ara-A and ara-ATP are observed in a protein-synthesizing, cell-free system isolated from L5178Y cells.
用完整细胞系统以及分离的酶系统测试了9-β-D-阿拉伯呋喃糖基腺嘌呤（ara-A）及其5'-三磷酸衍生物对程序性合成的影响。在小鼠淋巴瘤细胞（L5178Y）中测试了ara-A的作用。该化合物在低浓度下通过细胞停滞减少细胞增殖；在高ara-A浓度下，将放射性前体掺入DNA、RNA和蛋白质的情况表明ara-A选择性抑制DNA合成。多核糖体复合物的形成不受ara-A影响。[3H]ara-A在完整细胞系统中掺入DNA；每8000个脱氧腺苷分子中有1个ara-A分子掺入。大多数ara-A分子似乎处于核苷酸间连接中。未检测到ara-A掺入RNA。9-β-D-阿拉伯呋喃糖基腺嘌呤5'-三磷酸（ara-ATP）不会降低从鹌鹑输卵管分离的以下酶的掺入率：DNA依赖性RNA聚合酶I和II、聚腺苷酸聚合酶以及聚（二磷酸腺苷核糖）聚合酶。发现该化合物抑制从鹌鹑输卵管和致癌RNA病毒（劳氏肉瘤病毒）分离的DNA聚合酶催化的DNA合成。所有测试的酶都被ara-ATP以相对于脱氧腺苷5'-三磷酸的竞争性方式抑制。在真核低分子DNA依赖性DNA聚合酶的测定中发现ara-ATP的亲和力最高，即该药物的抑制效力最高。对真核高分子DNA依赖性DNA聚合酶的影响稍小。与真核DNA聚合酶相比，病毒酶（RNA指导的DNA聚合酶和DNA指导的DNA聚合酶）受ara-ATP的影响较小。在从L5178Y细胞分离的无细胞蛋白质合成系统中未观察到ara-A和ara-ATP的作用。
