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叠氮胞苷是3T6细胞中脱氧核糖核苷酸合成的特异性抑制剂。

Azidocytidine is a specific inhibitor of deoxyribonucleotide synthesis in 3T6 cells.

作者信息

Akerblom L, Reichard P

出版信息

J Biol Chem. 1985 Aug 5;260(16):9197-202.

PMID:4019469
Abstract

2'-Azidocytidine is a specific inhibitor of DNA synthesis in cultured 3T6 mouse fibroblasts. Earlier work (Akerblom, L., Pontis, E., and Reichard, P. (1982) 257, 6776-6782) indicated that the nucleoside, after phosphorylation, acted by inhibiting both ribonucleotide reduction and DNA strand elongation. We now demonstrate that the effect on strand elongation was due to a contamination of azidocytidine with less than 0.3% of arabinosyl cytosine. Pure azidocytidine inhibits specifically ribonucleotide reductase and its effects on DNA synthesis are secondary to this inhibition. The results with azidocytidine concerning the size and turnover of deoxyribonucleoside triphosphate pools parallel those of hydroxyurea and are distinct from those of arabinosyl cytosine. Together with hydroxyurea, azidocytidine is a useful compound in studies aiming at a specific block of the production of deoxynucleoside triphosphates in intact cells. Comparisons of the effects of azidocytidine and arabinosyl cytosine complement earlier studies with hydroxyurea and aphidicolin concerning inter-relations between dNTP synthesis and DNA replication.

摘要

2'-叠氮胞苷是培养的3T6小鼠成纤维细胞中DNA合成的特异性抑制剂。早期研究(阿克布洛姆,L.,庞蒂斯,E.,和赖夏德,P.(1982年)257,6776 - 6782)表明,该核苷磷酸化后通过抑制核糖核苷酸还原和DNA链延伸发挥作用。我们现在证明,对链延伸的影响是由于叠氮胞苷被低于0.3%的阿糖胞苷污染所致。纯叠氮胞苷特异性抑制核糖核苷酸还原酶,其对DNA合成的影响是这种抑制的继发效应。关于脱氧核苷三磷酸池的大小和周转,叠氮胞苷的结果与羟基脲的结果相似,与阿糖胞苷的结果不同。与羟基脲一起,叠氮胞苷是旨在特异性阻断完整细胞中脱氧核苷三磷酸产生的研究中的一种有用化合物。叠氮胞苷和阿糖胞苷作用的比较补充了早期关于羟基脲和阿非科林对dNTP合成与DNA复制之间相互关系的研究。

相似文献

1
Azidocytidine is a specific inhibitor of deoxyribonucleotide synthesis in 3T6 cells.叠氮胞苷是3T6细胞中脱氧核糖核苷酸合成的特异性抑制剂。
J Biol Chem. 1985 Aug 5;260(16):9197-202.
2
Effects of azidocytidine on DNA synthesis and deoxynucleotide pools of mouse fibroblast cell lines.
J Biol Chem. 1982 Jun 25;257(12):6776-82.
3
Relations between synthesis of deoxyribonucleotides and DNA replication in 3T6 fibroblasts.
J Biol Chem. 1985 May 10;260(9):5376-81.
4
Effects of cytosine arabinoside and hydroxyurea on the synthesis of deoxyribonucleotides and DNA replication in L1210 cells.阿糖胞苷和羟基脲对L1210细胞中脱氧核糖核苷酸合成及DNA复制的影响。
Adv Enzyme Regul. 1990;30:47-59. doi: 10.1016/0065-2571(90)90008-p.
5
2'-Deoxy-2'-azidocytidine, a new inhibitor of DNA replication in mammalian cells.
Eur J Biochem. 1977 Jan;72(2):371-8. doi: 10.1111/j.1432-1033.1977.tb11261.x.
6
Evidence for the involvement of substrate cycles in the regulation of deoxyribonucleoside triphosphate pools in 3T6 cells.关于底物循环参与3T6细胞中脱氧核糖核苷三磷酸库调节的证据。
J Biol Chem. 1985 Aug 5;260(16):9216-22.
7
On the regulation of deoxyribonucleotide synthesis.
Curr Top Cell Regul. 1985;26:403-9. doi: 10.1016/b978-0-12-152826-3.50038-3.
8
Azidocytidine is incorporated into RNA of 3T6 mouse fibroblasts.叠氮胞苷被掺入3T6小鼠成纤维细胞的RNA中。
FEBS Lett. 1985 Dec 2;193(2):203-7. doi: 10.1016/0014-5793(85)80151-4.
9
Interrelations between substrate cycles and de novo synthesis of pyrimidine deoxyribonucleoside triphosphates in 3T6 cells.3T6细胞中底物循环与嘧啶脱氧核糖核苷三磷酸从头合成之间的相互关系。
Proc Natl Acad Sci U S A. 1986 Feb;83(4):986-90. doi: 10.1073/pnas.83.4.986.
10
Deoxyribonucleotide pools in mouse-fibroblast cell lines with altered ribonucleotide reductase.核糖核苷酸还原酶改变的小鼠成纤维细胞系中的脱氧核糖核苷酸池
Eur J Biochem. 1976 Dec;71(1):39-43. doi: 10.1111/j.1432-1033.1976.tb11087.x.

引用本文的文献

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Cell- and Polymerase-Selective Metabolic Labeling of Cellular RNA with 2'-Azidocytidine.用 2'-叠氮胞苷对细胞 RNA 进行细胞和聚合酶选择性代谢标记。
J Am Chem Soc. 2020 Aug 26;142(34):14417-14421. doi: 10.1021/jacs.0c04566. Epub 2020 Aug 14.
2
Cellular delivery of nucleoside diphosphates: a prodrug approach.核苷二磷酸的细胞递送:一种前药方法。
Pharm Res. 1997 Jun;14(6):706-12. doi: 10.1023/a:1012133902314.
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Inhibition of ribonucleotide reductase by 2'-substituted deoxycytidine analogs: possible application in AIDS treatment.
2'-取代脱氧胞苷类似物对核糖核苷酸还原酶的抑制作用:在艾滋病治疗中的可能应用。
Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8403-7. doi: 10.1073/pnas.91.18.8403.
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Interrelations between substrate cycles and de novo synthesis of pyrimidine deoxyribonucleoside triphosphates in 3T6 cells.3T6细胞中底物循环与嘧啶脱氧核糖核苷三磷酸从头合成之间的相互关系。
Proc Natl Acad Sci U S A. 1986 Feb;83(4):986-90. doi: 10.1073/pnas.83.4.986.
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Deoxyadenosine reverses hydroxyurea inhibition of vaccinia virus growth.脱氧腺苷可逆转羟基脲对痘苗病毒生长的抑制作用。
J Virol. 1991 May;65(5):2290-8. doi: 10.1128/JVI.65.5.2290-2298.1991.