Wanstall Hannah C, Henthorn Nicholas T, Jones James, Santina Elham, Chadwick Amy L, Angal-Kalinin Deepa, Morris Geoffrey, Warmenhoven John-William, Smith Rob, Mathisen Storm, Merchant Michael J, Jones Roger M
Department of Physics and Astronomy, Faculty of Science and Engineering, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.
J Radiat Res. 2023 May 6;64(3):547-57. doi: 10.1093/jrr/rrad032.
The pBR322 plasmid DNA was irradiated with 35 MeV electrons, 228 MeV protons and 300 kVp X-rays to quantify DNA damage and make comparisons of DNA damage between radiation modalities. Plasmid was irradiated in a medium containing hydroxyl radical scavengers in varying concentrations. This altered the amount of indirect hydroxyl-mediated DNA damage, to create an environment that is more closely associated with a biological cell. We show that increasing hydroxyl scavenger concentration significantly reduced post-irradiation DNA damage to pBR322 plasmid DNA consistently and equally with three radiation modalities. At low scavenging capacities, irradiation with both 35 MeV electrons and 228 MeV protons resulted in increased DNA damage per dose compared with 300 kVp X-rays. We quantify both single-strand break (SSB) and double-strand break (DSB) induction between the modalities as a ratio of yields relative to X-rays, referred to as relative biological effectiveness (RBE). RBESSB values of 1.16 ± 0.15 and 1.18 ± 0.08 were calculated for protons and electrons, respectively, in a low hydroxyl scavenging environment containing 1 mM Tris-HCl for SSB induction. In higher hydroxyl scavenging capacity environments (above 1.1 × 106 s-1), no significant differences in DNA damage induction were found between radiation modalities when using SSB induction as a measure of RBE. Considering DSB induction, significant differences were only found between X-rays and 35 MeV electrons, with an RBEDSB of 1.72 ± 0.91 for 35 MeV electrons, indicating that electrons result in significantly more SSBs and DSBs per unit of dose than 300 kVp X-rays.
用35兆电子伏特的电子、228兆电子伏特的质子和300千伏峰值的X射线照射pBR322质粒DNA,以量化DNA损伤并比较不同辐射方式之间的DNA损伤情况。质粒在含有不同浓度羟基自由基清除剂的介质中进行照射。这改变了间接羟基介导的DNA损伤量,营造了一个与生物细胞更密切相关的环境。我们发现,增加羟基清除剂浓度可显著降低照射后pBR322质粒DNA的损伤,且三种辐射方式的降低效果一致且相同。在低清除能力下,与300千伏峰值的X射线相比,用35兆电子伏特的电子和228兆电子伏特的质子照射时,每剂量的DNA损伤增加。我们将不同方式之间单链断裂(SSB)和双链断裂(DSB)的诱导情况量化为相对于X射线的产率比值,称为相对生物效能(RBE)。在含有1毫摩尔/升Tris-HCl的低羟基清除环境中,对于SSB诱导,质子和电子的RBE SSB值分别计算为1.16±0.15和1.18±0.08。在较高的羟基清除能力环境(高于1.1×106秒-1)中,当以SSB诱导作为RBE的衡量指标时,未发现不同辐射方式之间的DNA损伤诱导存在显著差异。考虑DSB诱导时,仅发现X射线与35兆电子伏特的电子之间存在显著差异,35兆电子伏特的电子的RBE DSB为1.72±0.91,这表明电子每单位剂量产生的SSB和DSB比300千伏峰值的X射线显著更多。