Supplementary Material for: Cell and Tissue Damage after Skin Exposure to Ionizing Radiation: Short- and Long-Term Effects after a Single and Fractional Doses

Ionizing radiation is often used to treat progressive neoplasms. However, the consequences of long-term radiation exposure to healthy skin tissue are poorly understood. We aimed to evaluate the short- and long-term radiation damage to healthy skin of the same irradiation given either as single or fractional doses. C57BL/J6 mice were randomly assigned to one of three groups: a control and two exposure groups (5 Gy ×2 or 10 Gy ×1). The inguinal area was irradiated (6-MeV beam) 1 week after depilation in the treatment groups. Skin samples were evaluated macroscopically and histologically for up to 6 months after the final exposure. After anagen hair follicle injury by irradiation, hair cycling resumed in both groups, but hair graying was observed in the 10 Gy ×1 group but not in the 5 Gy ×2 group, suggesting the dose of each fractional exposure is more relevant to melanocyte stem cell damage than the total dose. On the other hand, in the long term, the fractional double exposures induced more severe atrophy and capillary reduction in the dermis and subcutis, suggesting fractional exposure may cause more depletion of tissue stem cells and endothelial cells in the tissue. Thus, our results indicated that there were differences between the degrees of damage that occurred as a result of a single exposure compared with fractional exposures to ionizing radiation: the former induces more severe acute injury to the skin with irreversible depigmentation of hairs, while the latter induces long-term damage to the dermis and subcutis.

电离辐射（Ionizing radiation）常被用于治疗进展期肿瘤。然而，目前学界对健康皮肤组织长期暴露于辐射所产生的不良影响仍知之甚少。本研究旨在评估相同总辐射剂量分别采用单次照射与分割照射两种方式时，对健康皮肤造成的短期与长期辐射损伤。我们将C57BL/J6小鼠随机分为三组：对照组与两个照射组（分别为5 Gy×2次组与10 Gy×1次组）。处理组小鼠在脱毛1周后，对其腹股沟区域采用6-MeV射线束进行照射。于末次照射后长达6个月的周期内，从宏观观测与组织病理学层面评估皮肤样本。照射造成生长期毛囊损伤后，两组小鼠均恢复了毛发周期，但10 Gy×1次组出现了毛发变白现象，而5 Gy×2次组未出现该现象，这提示单次分割照射剂量较总辐射剂量更与黑素细胞干细胞（melanocyte stem cell）损伤相关。另一方面，从长期来看，两次分割照射组在真皮层与皮下组织中出现了更严重的萎缩与毛细血管减少现象，提示分割照射可能会更显著地耗竭组织中的组织干细胞与内皮细胞。综上，本研究结果表明，单次照射与分割照射两种电离辐射方式所造成的皮肤损伤程度存在显著差异：前者会对皮肤造成更严重的急性损伤，并引发毛发不可逆性色素脱失；而后者则会对真皮层与皮下组织造成长期损伤。