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3-氨基苯甲酰胺通过干扰嘌呤生物合成途径对野生型和6-硫鸟嘌呤抗性中国仓鼠细胞的差异毒性。

Differential toxicity of 3-aminobenzamide to wild-type and 6-thioguanine-resistant Chinese hamster cells by interference with pathways of purine biosynthesis.

作者信息

Cleaver J E

出版信息

Mutat Res. 1984 Mar-Apr;131(3-4):123-7. doi: 10.1016/0167-8817(84)90051-8.

DOI:10.1016/0167-8817(84)90051-8
PMID:6717467
Abstract

3-Aminobenzamide is commonly assumed to be a specific inhibitor of poly(ADP-ribose) polymerase. However, it also inhibits de novo synthesis of DNA purines at concentrations of 5 mM and above. A mutant cell line that lacks the ability to incorporate exogenous purines is therefore exceptionally sensitive to the toxic effects of 3-aminobenzamide. This finding has implications for the underlying mechanism of sensitivity to 3-aminobenzamide recently reported in a cell line from an immunodeficient patient, and also implies that many studies using high concentrations of 3-aminobenzamide may not demonstrate a role for poly(ADP-ribose) because of artifacts arising from disturbance of intracellular purine metabolism.

摘要

3-氨基苯甲酰胺通常被认为是聚(ADP-核糖)聚合酶的特异性抑制剂。然而,在浓度为5 mM及以上时,它也会抑制DNA嘌呤的从头合成。因此,一种缺乏整合外源性嘌呤能力的突变细胞系对3-氨基苯甲酰胺的毒性作用异常敏感。这一发现对最近报道的来自免疫缺陷患者的细胞系中对3-氨基苯甲酰胺敏感性的潜在机制具有启示意义,也意味着许多使用高浓度3-氨基苯甲酰胺的研究可能无法证明聚(ADP-核糖)的作用,因为细胞内嘌呤代谢紊乱会产生假象。

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引用本文的文献

1
Inhibitors and activators of ADP-ribosylation reactions.ADP核糖基化反应的抑制剂和激活剂。
Mol Cell Biochem. 1994 Sep;138(1-2):185-97. doi: 10.1007/BF00928461.
2
Analysis of bromodeoxyuridine-induced single and twin sister chromatid exchanges in tetraploid Chinese hamster ovary cells.溴脱氧尿苷诱导四倍体中国仓鼠卵巢细胞单和双姐妹染色单体交换的分析
Chromosoma. 1986;93(5):409-12. doi: 10.1007/BF00285822.