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2'-叠氮多核苷酸对致癌病毒功能的抑制作用。

Inhibition of oncornavirus functions by 2'-azido polynucleotides.

作者信息

De Clercq E, Billiau A, Hobbs J, Torrence P F, Witkop B

出版信息

Proc Natl Acad Sci U S A. 1975 Jan;72(1):284-8. doi: 10.1073/pnas.72.1.284.

Abstract

The 2'-azido analogs of poly(U) and poly(C), poly(dUz) [poly(2'-azido-2'-deoxyuridylic acid)], and poly-(dCz [poly(2'-azido-2'-deoxycytidylic acid)], were found to inhibit the RNA-directed DNA polymerase (reverse transcriptase) activity of murine leukemia (Moloney, Rauscher) and sarcoma (Moloney) virus, and feline leukemia (Theilen) and sarcoma (Gardner) virus, while under the same conditions the unsubstituted parent compounds failed to do so. In addition, poly(dUz) and poly(dCz) inhibited the replication of exogenous murine sarcoma virus (Moloney) in nontransformed cells (as assessed by an infectious center assay), but poly(dUz) failed to suppress the formation of endogenous sarcoma and leukemia viruses in transformed cell lines (MO-P, JLSV5). In these same cells, poly(dUz) failed to inhibit the multiplication of vesicular stomatitis virus. These data add further strength to the contention that reverse transcriptase is necessary for the productive infection and transformation of normal cells by oncornaviruses but is not essential maintenance of this transformed state and the continuous production of new viruses particles by these transformed cells.

摘要

已发现聚(U)和聚(C)的2'-叠氮类似物,即聚(dUz)[聚(2'-叠氮-2'-脱氧尿苷酸)]和聚(dCz)[聚(2'-叠氮-2'-脱氧胞苷酸)],能抑制小鼠白血病(莫洛尼、劳舍尔)病毒、肉瘤(莫洛尼)病毒、猫白血病(泰伦)病毒和肉瘤(加德纳)病毒的RNA指导的DNA聚合酶(逆转录酶)活性,而在相同条件下未取代的母体化合物则无此作用。此外,聚(dUz)和聚(dCz)抑制非转化细胞中外源小鼠肉瘤病毒(莫洛尼)的复制(通过感染中心试验评估),但聚(dUz)未能抑制转化细胞系(MO-P、JLSV5)中内源性肉瘤和白血病病毒的形成。在这些相同的细胞中,聚(dUz)未能抑制水疱性口炎病毒的增殖。这些数据进一步支持了以下论点:逆转录酶对于肿瘤病毒对正常细胞的有效感染和转化是必需的,但对于维持这些转化细胞的这种转化状态和持续产生新病毒颗粒并非必不可少。

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Viruses, polymerases, and cancer.病毒、聚合酶与癌症。
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