Azapyrimidine analogues: inhibition of viral DNA synthesis and protein synthesis in SV40 infected BSC-1 cells.

Azapyrimidine analogues: inhibition of viral DNA synthesis and protein synthesis in SV40 infected BSC-1 cells.
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氮杂嘧啶类似物:抑制 SV40 感染的 BSC-1 细胞中的病毒 DNA 合成和蛋白质合成。

DOI:
10.1007/bf02620813
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发表时间:
1988
期刊:
In vitro cellular & developmental biology : journal of the Tissue Culture Association
影响因子:
--
通讯作者:
Albury,D
Albury,D
中科院分区:
--
文献类型:
--
作者:
Johnson-Thompson,M;Albury,D

文献摘要

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用5,6-二氢-5-氮杂胞苷(DH-5-AzaCR)或5-氮杂胞苷(5-AzaCR)处理BSC-1细胞后,体外分析猴病毒40 DNA和蛋白质合成的复制。结果表明,在100 μg/ml处理3小时后,DH-5-AzaCR显示出77%的病毒DNA合成抑制,而5-AzaCR导致50%的抑制。当用低剂量(0.1至0.5 μg/ml)5-AzaCR处理感染的培养物3小时以及用100 μg/ml 5-AzaCR处理1小时和2小时后,DNA合成受到刺激;然而,DH-5-AzaCR没有刺激。当在琼脂糖凝胶上分析时,在任一药物存在下合成的DNA表现出改变的构象;然而,在DH-5-AzaCR处理后,这种改变可以忽略不计,但在5-AzaCR存在下更明显。限制性内切酶分析表明,DH-5-AzaCR可能不是5-AzaCR那样的低甲基化剂。在用DH-5-AzaCR处理后6小时,总蛋白质合成(细胞和病毒)的抑制基本上完全,而5-AzaCR在3小时后完全抑制蛋白质合成。这些数据表明,5-AzaCR对DNA合成的抑制没有表现出直接的剂量关系,而DH-5-AzaCR可能表现出一定的剂量关系,并且与5-AzaCR相比,DH-5-AzaCR是更有效的DNA合成抑制剂。
The replication of simian virus 40 DNA and protein synthesis in BSC-1 cells was analyzed in vitro after treatment with 5,6-dihydro-5-azacytidine (DH-5-AzaCR) or 5-azacytidine (5-AzaCR). Results demonstrated that after a 3-h treatment period with 100 μg/ml, DH-5-AzaCR exhibited a 77% inhibition of viral DNA synthesis, whereas 5-AzaCR resulted in a 50% inhibition. Stimulation of DNA synthesis occurred when infected cultures were treated with low doses (0.1 to 0.5 μg/ml) of 5-AzaCR for 3h and after 1 and 2 h of treatment with 100 μg/ml of 5-AzaCR; however, stimulation did not occur with DH-5-AzaCR. DNA synthesized in the presence of either drug demonstrated altered conformations when analyzed on agarose gels; however this alteration was negligible after DH-5-AzaCR treatment, but more pronounced in the presence of 5-AzaCR. Restriction enzyme analysis suggests that DH-5-AzaCR may not be a hypomethylating agent as is 5-AzaCR. Inhibition of total protein synthesis (cellular and viral) was essentially complete 6 h after treatment with DH-5-AzaCR, whereas 5-AzaCR completely inhibited protein synthesis after 3 h. These data indicate that 5-AzaCR does not exhibit a direct dose relationship to the inhibition of DNA synthesis whereas DH-5-AzaCR may show some dose relationship, and that DH-5-AzaCR is a more potent inhibitor of DNA synthesis as compared to 5-AzaCR.