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(阿糖胞苷)DNA在碱性条件下的不稳定性。

Instability of (ara-C) DNA under alkaline conditions.

作者信息

Major P P, Egan E M, Herrick D, Kufe D W

出版信息

Biochem Pharmacol. 1982 Mar 1;31(5):861-6. doi: 10.1016/0006-2952(82)90475-0.

DOI:10.1016/0006-2952(82)90475-0
PMID:7200770
Abstract

We employed both [5-3H] ara-C and ([2-14C] ara-C labeled L1210 DNA for analysis following exposure to alkali under various conditions. The results demonstrated that the tritium label on C5 of ara-C molecules incorporated in DNA was exchanged with water under alkaline conditions and, therefore, radioactivity was subsequently detectable in the acid-soluble fraction. The [14C] ara-C labeled DNA, however, was not susceptible to loss or radioactivity by this mechanism, and the appearance of this isotope in the acid-soluble fraction required degradation of the DNA strand or pyrimidine ring. Our results indicated that the [14C] labeled DNA was degraded by alkali, suggesting structural instability of this abnormal nucleic acid. These findings provide useful technical information on the purification of (ara-C) DNA labeled with different isotopes.

摘要

我们使用[5-³H]阿糖胞苷和([2-¹⁴C]阿糖胞苷标记的L1210 DNA,在各种条件下碱处理后进行分析。结果表明,掺入DNA中的阿糖胞苷分子C5上的氚标记在碱性条件下与水发生交换,因此,随后在酸溶性部分可检测到放射性。然而,[¹⁴C]阿糖胞苷标记的DNA不会因这种机制而损失放射性,该同位素在酸溶性部分的出现需要DNA链或嘧啶环的降解。我们的结果表明,[¹⁴C]标记的DNA被碱降解,表明这种异常核酸的结构不稳定。这些发现为不同同位素标记的(阿糖胞苷)DNA的纯化提供了有用的技术信息。

相似文献

1
Instability of (ara-C) DNA under alkaline conditions.(阿糖胞苷)DNA在碱性条件下的不稳定性。
Biochem Pharmacol. 1982 Mar 1;31(5):861-6. doi: 10.1016/0006-2952(82)90475-0.
2
Alkali lability of deoxyribonucleic acid that contains adenine arabinoside.
Biochem Pharmacol. 1983 Dec 15;32(24):3849-52. doi: 10.1016/0006-2952(83)90159-4.
3
Correlation of cytotoxicity with incorporation of ara-C into DNA.细胞毒性与阿糖胞苷掺入DNA的相关性。
J Biol Chem. 1980 Oct 10;255(19):8997-900.
4
Mechanistic implications of alterations in HL-60 cell nascent DNA after exposure to 1-beta-D-arabinofuranosylcytosine.暴露于1-β-D-阿拉伯呋喃糖基胞嘧啶后HL-60细胞新生DNA改变的机制意义
Cancer Chemother Pharmacol. 1992;31(1):61-70. doi: 10.1007/BF00695996.
5
Effect of ARA-C incorporation on deoxyribonucleic acid synthesis in cells.
Biochem Pharmacol. 1982 Sep 15;31(18):2937-40. doi: 10.1016/0006-2952(82)90266-0.
6
Metabolism and selective effects of 1-beta-D-arabinofuranosylcytosine in L1210 and Host tissues in vivo.1-β-D-阿拉伯呋喃糖基胞嘧啶在L1210及宿主体内组织中的代谢与选择性作用
Cancer Res. 1975 Jan;35(1):225-36.
7
Effects of 1-beta-D-arabinofuranosylcytosine incorporation on eukaryotic DNA template function.1-β-D-阿拉伯呋喃糖基胞嘧啶掺入对真核生物DNA模板功能的影响。
Mol Pharmacol. 1984 Jul;26(1):128-34.
8
Determinants of Ara-C action: biochemical consideration.阿糖胞苷作用的决定因素:生化方面的考量
Prog Clin Biol Res. 1983;132E:107-20.
9
DNA strand breaks caused by inhibitors of DNA synthesis: 1-beta-D-arabinofuranosylcytosine and aphidicolin.由DNA合成抑制剂导致的DNA链断裂:1-β-D-阿拉伯呋喃糖基胞嘧啶和阿非迪霉素。
Cancer Res. 1982 Oct;42(10):4050-3.
10
Studies on the mechanism of action of cytosine arabinoside.
Med Pediatr Oncol. 1982;10 Suppl 1:49-67. doi: 10.1002/mpo.2950100708.

引用本文的文献

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DNA Methyltransferases Demonstrate Reduced Activity against Arabinosylcytosine: Implications for Epigenetic Instability in Acute Myeloid Leukemia.DNA甲基转移酶对阿糖胞苷的活性降低:对急性髓系白血病表观遗传不稳定性的影响。
Biochemistry. 2017 Apr 25;56(16):2166-2169. doi: 10.1021/acs.biochem.7b00208. Epub 2017 Apr 12.
2
A phase I-II study of combination therapy with thymidine and cytosine arabinoside.一项关于胸苷与阿糖胞苷联合治疗的I-II期研究。
Cancer Chemother Pharmacol. 1983;11(1):43-7. doi: 10.1007/BF00257416.
3
Chemical synthesis of DNA oligomers containing cytosine arabinoside.
含阿糖胞苷的DNA寡聚物的化学合成
Nucleic Acids Res. 1988 Oct 11;16(19):9165-76. doi: 10.1093/nar/16.19.9165.
4
A comparison of the effects of cytosine arabinoside and beta-lactams on DNA synthesis and cellular proliferation.阿糖胞苷与β-内酰胺类药物对DNA合成及细胞增殖影响的比较
Cell Biol Toxicol. 1986 Dec;2(4):531-9. doi: 10.1007/BF00117855.
5
Mechanistic implications of alterations in HL-60 cell nascent DNA after exposure to 1-beta-D-arabinofuranosylcytosine.暴露于1-β-D-阿拉伯呋喃糖基胞嘧啶后HL-60细胞新生DNA改变的机制意义
Cancer Chemother Pharmacol. 1992;31(1):61-70. doi: 10.1007/BF00695996.