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链黑菌素在共济失调毛细血管扩张症成纤维细胞中诱导的非计划DNA合成。

Unscheduled DNA synthesis induced by streptonigrin in ataxia telangiectasia fibroblasts.

作者信息

Taylor A M, Laher H B, Morgan G R

出版信息

Carcinogenesis. 1985 Jun;6(6):945-7. doi: 10.1093/carcin/6.6.945.

DOI:10.1093/carcin/6.6.945
PMID:4006084
Abstract

Streptonigrin is an antitumour antibiotic, which at low doses produces DNA strand breaks in cultured cells leading, e.g., to decreased colony-forming ability and decreased rates of DNA synthesis. At higher doses the drug can induce unscheduled DNA synthesis (UDS) presumably as a consequence of excision of large DNA adducts. Ataxia telangiectasia (A-T) cells are unusually sensitive to streptonigrin, but we show here that they can perform excision repair, as demonstrated by UDS, at the same level as normal cells following exposure to the drug. This result suggests that of the apparent two modes of action of streptonigrin it is the DNA strand-breaking capacity to which A-T cells are unusually sensitive. This is consistent with previous reports suggesting some form of DNA strand break in A-T cells is deficiently repaired.

摘要

链黑菌素是一种抗肿瘤抗生素,低剂量时可在培养细胞中产生DNA链断裂,例如导致集落形成能力下降和DNA合成速率降低。高剂量时,该药物可诱导DNA修复合成(UDS),这可能是切除大的DNA加合物的结果。共济失调毛细血管扩张症(A-T)细胞对链黑菌素异常敏感,但我们在此表明,它们能够进行切除修复,如UDS所示,在接触该药物后与正常细胞处于相同水平。这一结果表明,在链黑菌素明显的两种作用模式中,A-T细胞对其DNA链断裂能力异常敏感。这与之前的报道一致,即A-T细胞中某种形式的DNA链断裂修复不足。

相似文献

1
Unscheduled DNA synthesis induced by streptonigrin in ataxia telangiectasia fibroblasts.链黑菌素在共济失调毛细血管扩张症成纤维细胞中诱导的非计划DNA合成。
Carcinogenesis. 1985 Jun;6(6):945-7. doi: 10.1093/carcin/6.6.945.
2
Effects of the DNA strand-cleaving antitumor agent, streptonigrin, on ataxia telangiectasia cells.DNA链裂解抗肿瘤剂链黑菌素对共济失调毛细血管扩张症细胞的影响。
Cancer Res. 1983 Jun;43(6):2700-3.
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Testing the role of p53 in the expression of genetic instability and apoptosis in ataxia-telangiectasia.检测p53在共济失调毛细血管扩张症中基因不稳定性表达及细胞凋亡中的作用。
Int J Radiat Biol. 1994 Dec;66(6 Suppl):S141-9.
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Expression cloning of multiple human cDNAs that complement the phenotypic defects of ataxia-telangiectasia group D fibroblasts.多个可弥补毛细血管扩张性共济失调D组成纤维细胞表型缺陷的人类cDNA的表达克隆。
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Abnormal response of ataxia-telangiectasia cells to agents that break the deoxyribose moiety of DNA via a targeted free radical mechanism.共济失调毛细血管扩张症细胞对通过靶向自由基机制破坏DNA脱氧核糖部分的试剂的异常反应。
Carcinogenesis. 1983 Oct;4(10):1317-22. doi: 10.1093/carcin/4.10.1317.
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Expression of a dominant negative I kappa B-alpha modulates hypersensitivity of ataxia telangiectasia fibroblasts to streptonigrin-induced apoptosis.显性负性IκB-α的表达调节共济失调毛细血管扩张症成纤维细胞对链黑菌素诱导的细胞凋亡的超敏反应。
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Cancer Res. 1979 Mar;39(3):1046-50.

引用本文的文献

1
ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia.欧洲呼吸学会关于共济失调毛细血管扩张症多学科呼吸管理的声明。
Eur Respir Rev. 2015 Dec;24(138):565-81. doi: 10.1183/16000617.0066-2015.
2
Ataxia-telangiectasia: an inherited disorder of ionizing-radiation sensitivity in man. Progress in the elucidation of the underlying biochemical defect.共济失调毛细血管扩张症:一种人类遗传性电离辐射敏感障碍。潜在生化缺陷阐释的进展。
Hum Genet. 1987 Mar;75(3):197-208. doi: 10.1007/BF00281059.
3
Human DNA repair defects.人类DNA修复缺陷。
J Inherit Metab Dis. 1986;9 Suppl 1:69-84. doi: 10.1007/BF01800860.