Zunino F, Gambetta R, Di Marco A, Zaccara A, Luoni G
Cancer Res. 1975 Mar;35(3):754-60.
The effects of the anthracycline antiboties, daunomycin and adriamycin, on the DNA-directed activities of DNA polymerases from murine sarcoma virus, rat liver (high-molecular-weight species), Escherichia coli, and Micrococcus luteus were determined. Under all conditions tested, these compounds had greater inhibitory effect against the viral polymerase than against cellular polymerase. The inhibition of murine sarcoma virus DNA polymerase by daunomycin was competitive with respect to DNA. For viral DNA polymerase it was concluded that the inhibition was predominatly caused by the interaction of duanomycin with the primer-template DNA. Also, an appreciable reversal of the daunomycin-induced inhibition of this polymerase by an increase in Mg-2+ concentration is consistent with the conclusion derived by competition experiments. In contrast, the inhibition of both rat liver and M. luteus DNA polymerases was essentially noncompetitive with DNA. Also, bacterial enzymes wer e less sensitive to inhibition by these drugs than the virion polymerase. The strong and preferential inhibiton of viral DNA polymerase is discussed in relation to a differential sensitivity of normal as compared to tumor cells observed in some cell lines.
测定了蒽环类抗生素柔红霉素和阿霉素对来自鼠肉瘤病毒、大鼠肝脏（高分子量型）、大肠杆菌和藤黄微球菌的DNA聚合酶的DNA指导活性的影响。在所有测试条件下，这些化合物对病毒聚合酶的抑制作用比对细胞聚合酶的抑制作用更强。柔红霉素对鼠肉瘤病毒DNA聚合酶的抑制作用在DNA方面具有竞争性。对于病毒DNA聚合酶，可以得出结论，这种抑制主要是由柔红霉素与引物模板DNA的相互作用引起的。此外，通过增加Mg2+浓度可明显逆转柔红霉素对该聚合酶的抑制作用，这与竞争实验得出的结论一致。相比之下，柔红霉素对大鼠肝脏和藤黄微球菌DNA聚合酶的抑制作用在本质上对DNA是非竞争性的。此外，细菌酶对这些药物抑制作用的敏感性低于病毒体聚合酶。结合在某些细胞系中观察到的正常细胞与肿瘤细胞的差异敏感性，讨论了病毒DNA聚合酶的强烈且优先抑制作用。
