Institute of Anatomy, University of Bern, Bern, Switzerland.
Biomedical Beamline, European Synchrotron Radiation Facility, Grenoble, France; Joint Department of Physics, The Institute of Cancer Research and the Royal Marsden Hospital, London, United Kingdom.
Int J Radiat Oncol Biol Phys. 2018 Jul 1;101(3):680-689. doi: 10.1016/j.ijrobp.2018.02.007. Epub 2018 Feb 13.
To analyze the effects of micro-beam irradiation (MBI) on the normal tissues of the mouse ear.
Normal mouse ears are a unique model, which in addition to skin contain striated muscles, cartilage, blood and lymphatic vessels, and few hair follicles. This renders the mouse ear an excellent model for complex tissue studies. The ears of C57BL6 mice were exposed to MBI (50-μm-wide micro-beams, spaced 200 μm between centers) with peak entrance doses of 200, 400, or 800 Gy (at ultra-high dose rates). Tissue samples were examined histopathologically, with conventional light and electron microscopy, at 2, 7, 15, 30, and 240 days after irradiation (dpi). Sham-irradiated animals acted as controls.
Only an entrance dose of 800 Gy caused a significant increase in the thickness of both epidermal and dermal ear compartments seen from 15 to 30 dpi; the number of sebaceous glands was significantly reduced by 30 dpi. The numbers of apoptotic bodies and infiltrating leukocytes peaked between 15 and 30 dpi. Lymphatic vessels were prominently enlarged at 15 up to 240 dpi. Sarcomere lesions in striated muscle were observed after all doses, starting from 2 dpi; scar tissue within individual beam paths remained visible up to 240 dpi. Cartilage and blood vessel changes remained histologically inconspicuous.
Normal tissues such as skin, cartilage, and blood and lymphatic vessels are highly tolerant to MBI after entrance doses up to 400 Gy. The striated muscles appeared to be the most sensitive to MBI. Those findings should be taken into consideration in future micro-beam radiation therapy treatment schedules.
分析微束照射(MBI)对小鼠耳朵正常组织的影响。
正常小鼠耳朵是一种独特的模型,除皮肤外还包含横纹肌、软骨、血管和淋巴管,以及少量毛囊。这使得小鼠耳朵成为复杂组织研究的极佳模型。C57BL6 小鼠的耳朵暴露于 MBI(50μm 宽的微束,中心间距 200μm)下,峰值入口剂量为 200、400 或 800Gy(超高剂量率)。组织样本在照射后 2、7、15、30 和 240 天进行组织病理学检查,包括常规光镜和电子显微镜检查。假照射动物作为对照。
只有 800Gy 的入口剂量在 15 至 30 天内导致耳表皮和真皮腔厚度显著增加;30 天时皮脂腺数量显著减少。凋亡小体和浸润性白细胞的数量在 15 至 30 天内达到峰值。淋巴管在 15 至 240 天内明显增大。横纹肌中的肌节损伤在所有剂量下均于 2 天开始出现;单个射束路径内的瘢痕组织在 240 天内仍可见。软骨和血管变化在组织学上仍不明显。
在高达 400Gy 的入口剂量下,皮肤、软骨、血管和淋巴管等正常组织对 MBI 具有高度耐受性。横纹肌对 MBI 似乎最为敏感。这些发现应在未来的微束放射治疗治疗计划中加以考虑。