Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, United Kingdom.
Shonan Kamakura General Hospital, Kamakura 247-8533, Japan.
Radiat Res. 2020 Dec 1;194(6):698-706. doi: 10.1667/RADE-19-00018.1.
Spatially fractionated radiation therapy (SFRT) has been based on the delivery of a single high-dose fraction to a large treatment area that has been divided into several smaller fields, reducing the overall toxicity and adverse effects. Complementary microbeam studies have also shown an effective tissue-sparing effect (TSE) in various tissue types and species after spatially fractionated irradiation at the microscale level; however, the underlying biological mechanism remains elusive. In the current study, using the combination of an ex vivo mouse spermatogenesis model and high-precision X-ray microbeams, we revealed the significant TSE for maintaining spermatogenesis after spatially fractionated microbeam irradiation. We used the following ratios of the irradiated to nonirradiated areas: 50:50, 150:50 and 350:50 µm-slit, where approximately 50, 75 and 87.5% of the sample was irradiated (using center-to-center distances of 100, 200 and 400 µm, respectively). We found that the 50 and 75% micro-slit irradiated testicular tissues showed an almost unadulterated TSE for spermatogenesis, whereas the 87.5% micro-slit irradiated tissues showed an incomplete TSE. This suggests that the TSE efficiency for spermatogenesis is dependent on the size of the nonirradiated spermatogonial stem cell pool in the irradiated testicular tissues. In addition, there would be a spatiotemporal limitation of stem cell migration/competition, resulting in the insufficient TSE for 87.5% micro-slit irradiated tissues. These stem cell characteristics are essential for the accurate prediction of tissue-level responses during or after SFRT, indicating the clinical potential for achieving better outcomes while preventing adverse effects.
空间分割放射治疗（SFRT）基于将单次高剂量剂量递送至已分为几个较小野的大治疗区域，从而降低整体毒性和不良反应。补充的微束研究还表明，在微尺度水平上进行空间分割照射后，各种组织类型和物种中也具有有效的组织保护效应（TSE）；但是，潜在的生物学机制仍然难以捉摸。在当前的研究中，使用体外小鼠精子发生模型和高精度 X 射线微束的组合，我们揭示了空间分割微束照射后维持精子发生的明显 TSE。我们使用了以下照射到未照射区域的比率：50:50、150:50 和 350:50 µm狭缝，其中大约 50、75 和 87.5％的样本被照射（使用中心到中心的距离分别为 100、200 和 400 µm）。我们发现，50 和 75％微狭缝照射的睾丸组织对精子发生几乎具有未被破坏的 TSE，而 87.5％微狭缝照射的组织则显示出不完全的 TSE。这表明精子发生的 TSE 效率取决于照射睾丸组织中未照射精原干细胞池的大小。此外，干细胞迁移/竞争会存在时空限制，从而导致 87.5％微狭缝照射的组织中 TSE 不足。这些干细胞特征对于在 SFRT 期间或之后准确预测组织水平的反应至关重要，表明了在预防不良反应的同时实现更好结果的临床潜力。
