Effect of hydroxyl radical scavenging capacity on clustering of DNA damage

Effect of hydroxyl radical scavenging capacity on clustering of DNA damage
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DOI:
10.2307/3579517
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发表时间:
1997-10-01
期刊:
影响因子:
3.4
通讯作者:
Ward, JF
Ward, JF
中科院分区:
医学3区
文献类型:
--
作者:
Milligan, JR;Aguilera, JA;Ward, JF

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我们以前已经证明,硫醇N-(2 '-巯基乙基)-1,3-丙二胺(WR-1065)可以减弱与电离辐射相关的链断裂的形成。这种保护的机制主要是DNA自由基物质的还原,否则DNA自由基物质会减弱作为链断裂前体的DNA自由基物质的化学修复。我们已经观察到,在照射过程中羟基自由基清除剂的存在导致WR-1065减弱链断裂形成的能力降低。由于已知离子化合物会影响双阳离子WR-1065与聚阴离子DNA的结合,因此清除剂的作用最初归因于其极性性质,对WR-1065与DNA的相互作用具有类似的作用,而不是其清除羟基自由基的能力的结果。在研究了额外的清除剂后,我们现在得出结论,增加的羟基自由基清除能力确实在一定程度上减弱了链断裂前体的修复。对这一观察结果的可能解释是,清除能力的增加导致DNA上更大程度的自由基聚集,并且这些多个自由基的簇比单个自由基物种的修复更慢。(C)1997年,辐射研究协会。
We have shown previously that the thiol N-(2'-mercaptoethyl)-1,3-diaminopropane (WR-1065) can attenuate the formation of strand breaks associated with ionizing radiation. The mechanism of this protection is predominantly the reduction of DNA radical species which otherwise would attenuate the chemical repair of DNA radical species which are strand break precursors. We had observed that the presence of a hydroxyl radical scavenger during irradiation resulted in a decrease in the ability of WR-1065 to attenuate the formation of strand breaks. Since ionic compounds are known to affect the binding of the dicationic WR-1065 with the polyanion DNA, the effect of the scavenger was initially attributed to its polar nature having a similar effect on the interaction of WR-1065 with DNA, and not as a consequence of its ability to scavenge hydroxyl radicals. After examining additional scavengers, we now conclude that an increased hydroxyl radical scavenging capacity does attenuate the repair of strand break precursors to some extent. The probable explanation for this observation is that an increased scavenging capacity results in a greater degree of radical clustering on the DNA, and that these clusters of multiple radicals are repaired more slowly than are single radical species. (C) 1997 by Radiation Research Society.