Milligan J R, Aguilera J A, Wu C C, Paglinawan R A, Nguyen T T, Wu D, Ward J F
Department of Radiology, University of California at San Diego, La Jolla 92093-0610, USA.
Radiat Res. 1997 Oct;148(4):325-9.
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.
我们之前已经表明，硫醇N-(2'-巯基乙基)-1,3-二氨基丙烷（WR-1065）可以减轻与电离辐射相关的链断裂的形成。这种保护机制主要是减少DNA自由基种类，否则这些自由基会减弱作为链断裂前体的DNA自由基种类的化学修复。我们观察到，在辐照期间存在羟基自由基清除剂会导致WR-1065减轻链断裂形成的能力下降。由于已知离子化合物会影响二价阳离子WR-1065与多阴离子DNA的结合，清除剂的作用最初被归因于其极性性质对WR-1065与DNA相互作用有类似影响，而不是由于其清除羟基自由基的能力。在研究了其他清除剂之后，我们现在得出结论，增加的羟基自由基清除能力确实会在一定程度上减弱链断裂前体的修复。对这一观察结果的可能解释是，增加的清除能力导致DNA上自由基聚集程度更高，并且这些多个自由基的簇比单个自由基种类修复得更慢。
