The Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, 4-5 Little France Drive, Edinburgh, EH16 4UU, UK.
The Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, 4-5 Little France Drive, Edinburgh, EH16 4UU, UK.
Dis Model Mech. 2024 Aug 1;17(8). doi: 10.1242/dmm.050733. Epub 2024 Aug 22.
The salivary glands are often damaged during head and neck cancer radiotherapy. This results in chronic dry mouth, which adversely affects quality of life and for which there is no long-term cure. Mouse models of salivary gland injury are routinely used in regenerative research. However, there is no clear consensus on the radiation regime required to cause injury. Here, we analysed three regimes of γ-irradiation of the submandibular salivary gland. Transcriptional analysis, immunofluorescence and flow cytometry was used to profile DNA damage, gland architecture and immune cell changes 3 days after single doses of 10 or 15 Gy or three doses of 5 Gy. Irrespective of the regime, radiation induced comparable levels of DNA damage, cell cycle arrest, loss of glandular architecture, increased pro-inflammatory cytokines and a reduction in tissue-resident macrophages, relative to those observed in non-irradiated submandibular glands. Given these data, coupled with the fact that repeated anaesthetic can negatively affect animal welfare and interfere with saliva secretion, we conclude that a single dose of 10 Gy irradiation is the most refined method of inducing acute salivary gland injury in a mouse model.
唾液腺在头颈部癌症放疗中经常受损。这导致慢性口干，这会对生活质量产生不利影响，而且目前尚无长期治愈方法。唾液腺损伤的小鼠模型经常用于再生研究。然而，对于导致损伤所需的辐射方案尚未达成明确共识。在这里，我们分析了下颌下唾液腺的三种γ辐照方案。在单次剂量为 10 或 15Gy 或三次剂量为 5Gy 后 3 天，使用转录分析、免疫荧光和流式细胞术来描绘 DNA 损伤、腺体结构和免疫细胞变化。无论采用哪种方案，与未辐照的下颌下腺相比，辐射都会引起相当水平的 DNA 损伤、细胞周期停滞、腺体结构丧失、促炎细胞因子增加以及组织驻留巨噬细胞减少。考虑到这些数据，再加上重复麻醉会对动物福利产生负面影响并干扰唾液分泌这一事实，我们得出结论，单次 10Gy 剂量的辐照是在小鼠模型中诱导急性唾液腺损伤的最精细方法。
