Milligan J R, Ng J Y, Wu C C, Aguilera J A, Fahey R C, Ward J F
Department of Radiology, University of California at San Diego, La Jolla 92093-0610, USA.
Radiat Res. 1995 Sep;143(3):273-80.
Using agarose gel electrophoresis, we have measured the yields of DNA single- and double-strand breaks (SSBs and DSBs) for plasmid DNA gamma-irradiated in aerobic aqueous solution. The presence during irradiation of either of the thiols cysteamine or N-(2-thioethyl)-1,3-diaminopropane (WR-1065) resulted in a concentration-dependent decrease in the yield of SSBs and a much greater decrease in the yield of DSBs. This large differential protective effect was not produced by thioethers or an alcohol of structural similarity to the two thiols, suggesting that repair of DSB radical precursors by thiols is more efficient than for SSB precursors. These observations suggest the existence of a diradical intermediate in the formation of DSBs. The results argue against a major contribution by a single radical mechanism involving interstrand radical transfer via hydrogen abstraction by a peroxyl intermediate, since the half-life of this radical transfer reaction appears to be significantly greater than the lifetime of the intermediate.
利用琼脂糖凝胶电泳，我们测量了在有氧水溶液中经γ射线辐照的质粒DNA的单链和双链断裂（SSB和DSB）产量。在辐照过程中，半胱胺或N-(2-硫代乙基)-1,3-二氨基丙烷（WR-1065）这两种硫醇中的任何一种的存在，都会导致SSB产量呈浓度依赖性下降，而DSB产量下降幅度更大。这种巨大的差异保护作用不是由硫醚或与这两种硫醇结构相似的醇产生的，这表明硫醇对DSB自由基前体的修复比对SSB前体的修复更有效。这些观察结果表明在DSB形成过程中存在双自由基中间体。这些结果反对了一种涉及过氧中间体通过氢提取进行链间自由基转移的单自由基机制的主要贡献，因为这种自由基转移反应的半衰期似乎明显大于中间体的寿命。
