The clinical superiority of proton therapy over photon therapy has recently gained recognition; however, the biological effects of proton therapy remain poorly understood. The lack of in vivo evidence is especially important. Therefore, the goal of this study was to validate the usefulness of Drosophila melanogaster as an alternative tool in proton radiobiology. To determine whether the comparative biological effects of protons and X rays are detectable in Drosophila, we assessed their influence on survival and mRNA expression. Postirradiation observation revealed that protons inhibited their development and reduced the overall survival rates more effectively than X rays. The relative biological effectiveness of the proton beams compared to the X rays estimated from the 50% lethal doses was 1.31. At 2 or 24 h postirradiation, mRNA expression analysis demonstrated that the expression patterns of several genes (such as DNA-repair-, apoptosis- and angiogenesis-related genes) followed different time courses depending on radiation type. Moreover, our trials suggested that the knockdown of individual genes by the GAL4/UAS system changes the radiosensitivity in a radiation type-specific manner. We confirmed this Drosophila model to be considerably useful to evaluate the findings from in vitro studies in an in vivo system. Furthermore, this model has a potential to elucidate more complex biological mechanisms underlying proton irradiation.

中文翻译：

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果蝇，果蝇，作为研究质子辐照生物效应的体内工具。


质子治疗相对于光子治疗的临床优越性最近得到了认可。然而，人们对质子治疗的生物学效应仍知之甚少。缺乏体内证据尤为重要。因此，本研究的目的是验证黑腹果蝇作为质子放射生物学替代工具的有用性。为了确定在果蝇中是否可以检测到质子和 X 射线的比较生物学效应，我们评估了它们对存活和 mRNA 表达的影响。辐照后观察表明，质子比 X 射线更有效地抑制其发育并降低总体存活率。根据 50% 致死剂量估算，质子束与 X 射线的相对生物有效性为 1.31。辐射后 2 或 24 小时，mRNA 表达分析表明，根据辐射类型，多种基因（例如 DNA 修复、细胞凋亡和血管生成相关基因）的表达模式遵循不同的时间进程。此外，我们的试验表明，GAL4/UAS 系统对单个基因的敲低会以特定于辐射类型的方式改变放射敏感性。我们证实这种果蝇模型对于评估体内系统体外研究的结果非常有用。此外，该模型有可能阐明质子辐照背后更复杂的生物机制。