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放射防护性氨基硫醇WR 1065诱导的染色质结构构象变化

Conformational changes in chromatin structure induced by the radioprotective aminothiol, WR 1065.

作者信息

Vaughan A T, Grdina D J, Meechan P J, Milner A E, Gordon D J

机构信息

Division of Biological and Medical Research, Argonne National Laboratory, IL 60349.

出版信息

Br J Cancer. 1989 Dec;60(6):893-6. doi: 10.1038/bjc.1989.386.

DOI:10.1038/bjc.1989.386
PMID:2605099
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2247278/
Abstract

WR 1065, 2-[(minopropyl) amino] ethanethiol is an effective scavenger of free radicals. When present during irradiation it reduces cellular DNA damage as analysed by alkaline elution from filters. The same technique indicates that without irradiation, WR 1065 has no effect of DNA integrity. Using nucleoid analysis, where DNA damage is detected at the level of replicon clusters, WR 1065 distorts replicon supercoiling without breaking the DNA molecule. This confirmational change in nucleoid structure occurs with no detectable change in nucleoid protein content. It is proposed that perturbation of replicon supercoiling affects the process of normal DNA synthesis and strand break rejoining, allowing a longer time for the accurate repair of DNA damage.

摘要

WR 1065，即2-[(丙氨基)氨基]乙硫醇，是一种有效的自由基清除剂。在辐照过程中存在时，它能减少细胞DNA损伤，这是通过从滤膜上进行碱性洗脱分析得出的结果。同样的技术表明，在无辐照情况下，WR 1065对DNA完整性没有影响。使用核仁分析方法，即在复制子簇水平检测DNA损伤，WR 1065会使复制子超螺旋结构发生扭曲，但不会断裂DNA分子。核仁结构的这种构象变化发生时，核仁蛋白质含量没有可检测到的变化。有人提出，复制子超螺旋的扰动会影响正常DNA合成和链断裂重新连接的过程，从而为准确修复DNA损伤留出更长时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c68/2247278/9b1e00e45fbd/brjcancer00122-0091-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c68/2247278/9b1e00e45fbd/brjcancer00122-0091-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c68/2247278/9b1e00e45fbd/brjcancer00122-0091-a.jpg

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本文引用的文献

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Supercoiled loops and eucaryotic DNA replicaton.超螺旋环与真核生物DNA复制
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Evidence for two levels of DNA folding in histone-depleted HeLa interphase nuclei.在组蛋白缺失的HeLa间期细胞核中存在两级DNA折叠的证据。
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Amifostine: an update on its clinical status as a cytoprotectant in patients with cancer receiving chemotherapy or radiotherapy and its potential therapeutic application in myelodysplastic syndrome.氨磷汀：关于其在接受化疗或放疗的癌症患者中作为细胞保护剂的临床现状及其在骨髓增生异常综合征中的潜在治疗应用的最新情况。
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The effects of radioprotectors on DNA polymerase I-directed repair synthesis and DNA strand breaks in toluene-treated and X-irradiated Escherichia coli.辐射防护剂对经甲苯处理和X射线辐照的大肠杆菌中DNA聚合酶I介导的修复合成及DNA链断裂的影响。
Radiat Res. 1983 Jul;95(1):158-64.
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Rationale for initial clinical trials and future development of radioprotectors.
Cancer Clin Trials. 1980 Summer;3(2):165-73.
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Silver stain for proteins in polyacrylamide gels: a modified procedure with enhanced uniform sensitivity.聚丙烯酰胺凝胶中蛋白质的银染：一种具有增强均匀灵敏度的改良方法。
Anal Biochem. 1981 Nov 1;117(2):307-10. doi: 10.1016/0003-2697(81)90783-1.
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