Effect of isonicotinic acid hydrazide-copper complex on Rous sarcoma virus and its genome RNA

A. Antony, T. Ramakrishnan, Peter Mikelens, Jean Jackson, Warren Levinson
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引用次数: 12

Abstract

The copper complex of the antituberculous drug, isonicotinic acid hydrazide (INH), inhibits the RNA-dependent DNA polymerase of Rous sarcoma virus and inactivates its ability to malignantly transform chick embryo cells. The INH-copper complex binds to the 70S genome RNA of Rous sarcoma virus (RSV), which may account for its ability to inhibit the RNA-dependent DNA polymerase. The complex binds RNA more effectively than DNA in contrast to M-IBT-copper complexes, which bind both types of nucleic acids equally. The homopolymers, poly rA and poly rU, are bound by the INH-copper complex to a greater extent than poly rC. Isonicotinic acid hydrazide alone and CuSO4 alone bind neither DNA, RNA, poly (rA), poly (rU), nor poly (rC). However, CuSO4 alone binds poly (rI); INH alone does not.

In addition to viral DNA synthesis, chick-embryo cell DNA synthesis is inhibited by the INH-copper complex. The extent of inhibition of cellular DNA synthesis is greater than that of cellular RNA and protein synthesis. No selective inhibition of transformation in cells previously infected with Rous sarcoma virus is observed.

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异烟酸肼-铜复合物对劳斯肉瘤病毒及其基因组RNA的影响
抗结核药物异烟酸肼(INH)的铜复合物可抑制劳斯肉瘤病毒的rna依赖性DNA聚合酶,并使其无法恶性转化鸡胚细胞。INH-copper复杂结合70年代基因组RNA的劳斯氏肉瘤病毒(RSV),这也许可以解释其抑制依赖RNA的DNA聚合酶的能力。复杂的RNA结合更有效地比DNA M-IBT-copper复合物相比,这两种类型的核酸结合同样。均聚物聚rA和聚rU与inh -铜配合物的结合程度大于聚rC。异烟酸肼单独和CuSO4单独不结合DNA、RNA、聚(rA)、聚(rU)和聚(rC)。然而,CuSO4单独结合poly (rI);只有INH没有。除了病毒DNA合成外,INH-copper复合物还能抑制鸡胚细胞DNA合成。细胞DNA合成抑制的程度大于细胞RNA和蛋白质合成。在先前感染劳斯肉瘤病毒的细胞中,没有观察到选择性抑制转化。
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