Faggian Alessia, Pucci Gaia, Verroi Enrico, Fasolini Alberto, Lorentini Stefano, Citter Sara, Mione Maria Caterina, Calvaruso Marco, Russo Giorgio, Scifoni Emanuele, Forte Giusi Irma, Tommasino Francesco, Bisio Alessandra
Department of Physics, University of Trento, 38123 Trento, Italy.
Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, Italy.
Cancers (Basel). 2025 Aug 3;17(15):2564. doi: 10.3390/cancers17152564.
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).
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.
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.
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.
研究在常氧和低氧条件下，用常规剂量率和超高剂量率（UHDR）的质子束照射后，FLASH效应如何调节斑马鱼胚胎多个发育终点的辐射反应。
从成年斑马鱼获得胚胎，在受精后24小时（hpf）用228 MeV质子束以0.6和317 Gy/s的剂量率进行照射。对于低氧组，样品在照射前置于低氧箱内，而常氧组采用标准孵育。照射后，采集单个胚胎的图像，并在特定时间点评估辐射对幼虫长度、卵黄吸收、心包水肿、头部大小、眼睛大小和脊柱弯曲的影响。
数据表明，与传统照射方案相比，暴露于超高剂量率后毒性普遍显著降低，这在常氧和低氧条件下均保持。在常氧条件下，超高剂量率与传统照射引起的心包水肿水平存在显著差异，在低氧条件下，眼睛和头部大小存在显著差异。毒性评分分析显示超高剂量率有保护作用的趋势，这似乎与高分类别中胚胎的较低百分比有关。
在常氧（心包水肿）和低氧（头部和眼睛大小）条件下均观察到超高剂量率的辐射防护作用。这些结果表明，虽然超高剂量率可能具有减少辐射诱导损伤的潜力，但其保护作用取决于终点；氧合的作用也可能取决于所涉及的组织。
