辐射癌症治疗的超高剂量率（UHDR）曝光，所谓的FLASH放疗，似乎能够在不影响肿瘤对治疗的反应的同时减少正常组织的损伤。这项研究的目的是澄清一个问题，就是在UHDR为48.6 Gy/s的59.5 MeV质子束下，与传统剂量率（CONV）为0.057 Gy/s相比，是否能有效减少溶液中pBR322质粒DNA的DNA损伤。初始采用了pBR322质粒DNA在1×Tris-EDTA缓冲液中的简单系统进行质子束曝露。然后，我们使用了形胺基嘧啶-DNA酶（Fpg酶），将氧化嘌呤的氧化性碱基损伤转化为DNA链断裂，通过琼脂糖凝胶电泳来量化DNA单链断裂（SSB）和双链断裂（DSB）。 我们的研究结果显示，在UHDR下，SSB诱导率（每个质粒DNA/Gy的SSB）和Fpg酶敏感位点（ESS）的诱导显著降低，与CONV相比。然而，在DSB诱导和非-DSB聚类损伤方面没有显著差异。 59.5 MeV质子束的UHDR可以减少非聚类、非-DSB损伤，如SSB和稀疏分布的ESS。然而，这种效果可能在减少哺乳动物细胞的急性辐射效应和体内研究中才能显现致命的DNA损伤上不会显著。

Radiation cancer therapy with ultra-high dose rate (UHDR) exposure, so-called FLASH radiotherapy, appears to reduce normal tissue damage without compromising tumor response to therapy. The aim of this study was to clarify whether a 59.5 MeV proton beam at an UHDR of 48.6 Gy/s could effectively reduce the DNA damage of pBR322 plasmid DNA in solution compared to the conventional dose rate (CONV) of 0.057 Gy/s.A simple system, consisting of pBR322 plasmid DNA in 1× Tris-EDTA buffer, was initially employed for proton beam exposure. We then used formamidopyrimidine-DNA glycosylase (Fpg) enzymes. which convert oxidative base damages of oxidized purines to DNA strand breaks, to quantify DNA single strand breaks (SSBs) and double strand breaks (DSBs) by agarose gel electrophoresis.Our findings showed that the SSB induction rate (SSB per plasmid DNA/Gy) at UHDR and the induction of Fpg enzyme sensitive sites (ESS) were significantly reduced in UHDR compared to CONV. However, there was no significant difference in DSB induction and non-DSB cluster damages.UHDR of a 59.5 MeV proton beam could reduce non-clustered, non-DSB damages, such as SSB and sparsely distributed ESS. However, this effect may not be significant in reducing lethal DNA damage that becomes apparent only in acute radiation effects of mammalian cells and in vivo studies.