Amanda L Johnson, Sonia S Elder, John G McKendrick, Lizi M Hegarty, Ella Mercer, Elaine Emmerson
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引用次数: 0
摘要
头颈部癌症放疗常常会损伤唾液腺。这将导致长期口干,对生活质量造成不利影响,目前尚无长期治愈方法。唾液腺损伤小鼠模型被常规用于再生研究。然而,对于造成损伤所需的辐射机制还没有明确的共识。在这里,我们分析了对颌下腺进行伽马射线照射的三种方案。我们使用转录分析、免疫荧光和流式细胞术分析了单剂量 10 Gy、15 Gy 或 3 剂量 5 Gy 照射 3 天后的 DNA 损伤、腺体结构和免疫细胞变化。与未受辐照的颌下腺相比,无论采用哪种辐照机制,辐射都会诱发相似的 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。鉴于这些数据,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的事实,我们得出结论:单剂量 10 Gy 照射是在小鼠模型中诱导急性唾液腺损伤的最有效方法。
A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation.
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.
期刊介绍:
Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.