Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved.
目的：研究在常氧与缺氧条件下，斑马鱼胚胎经常规与超高剂量率（UHDR）质子束照射后，FLASH效应如何调控其对多种发育终点指标的辐射反应。方法：从成年斑马鱼获取胚胎，于受精后24小时（hpf）使用228 MeV质子束以0.6 Gy/s和317 Gy/s的剂量率进行照射。缺氧组样本在照射前置于缺氧舱内处理，常氧组则采用标准培养条件。照射后采集单个胚胎图像，并在特定时间点评估辐射对幼体体长、卵黄吸收、心包水肿、头部大小、眼部大小及脊柱弯曲度的影响。结果：数据显示，与常规剂量率照射相比，超高剂量率照射后的毒性显著降低，这一趋势在常氧与缺氧条件下均得以保持。在常氧条件下，超高剂量率与常规照射诱发的心包水肿程度存在显著差异；在缺氧条件下，眼部与头部大小的差异具有显著性。毒性评分分析表明超高剂量率具有保护性效应趋势，表现为高评分类别胚胎比例降低。结论：在常氧（心包水肿）与缺氧（头部及眼部大小）条件下均观察到超高剂量率的辐射保护效应。这些结果提示，虽然超高剂量率可能具备减轻辐射损伤的潜力，但其保护作用具有终点依赖性；氧合状态的作用也可能因所涉组织类型而异。
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