Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Applied and Translational Radiobiology, Medical University/AKH Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Department of Radiation Oncology, Kartal Dr. Lutfi Kırdar Training and Research Hospital, Health Science University, Istanbul, Turkey.
Strahlenther Onkol. 2018 Aug;194(8):771-779. doi: 10.1007/s00066-018-1302-6. Epub 2018 Apr 19.
During head and neck cancer treatment, the radiation response of the oral mucosa represents a frequent early side effect. Besides radiation-induced inhibition of proliferation, various other cellular responses occur. The radiation response of adherens and tight junction proteins was so far mostly investigated with large single-dose irradiation protocols, in vivo and in vitro. Therefore, the current study was initiated to investigate the impact of daily fractionated irradiation on the expression of adherens and tight junction proteins in vivo.
Fractionation with 5 × 3 Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 5 animals per day were euthanized every second day between day 0 (unirradiated controls) and day 14, and their tongues subjected to histological processing. Adherens junction marker (β-catenin and E‑cadherin) and tight junction marker (claudin-1 and occludin) expression was analysed in the oral mucosa of unirradiated controls and during two weeks of fractionated irradiation.
Adherens as well as tight junction marker proteins were rapidly and consistently upregulated in both the germinal as well as the functional layer of the oral mucosa. This represents a previously unknown parameter of the epithelial radiation response to clinically relevant fractionation protocols.
Fractionated irradiation significantly enhanced the expression of all proteins investigated. This study revealed a new parameter of the epithelial radiation response to fractionated irradiation.
在头颈部癌症治疗过程中,口腔黏膜的辐射反应是一种常见的早期副作用。除了辐射诱导的增殖抑制外,还会发生各种其他细胞反应。黏附连接和紧密连接蛋白的辐射反应迄今为止主要是使用大剂量单次照射方案,在体内和体外进行研究的。因此,本研究旨在研究每日分割照射对体内黏附连接和紧密连接蛋白表达的影响。
每周 5 次,每次 3 Gy(第 0-4 天和第 7-11 天)对小鼠的鼻部进行分割照射。每天一组 5 只动物,在第 0 天(未照射对照)至第 14 天之间每隔一天处死,对其舌头进行组织学处理。在未照射对照和两周分割照射期间,分析口腔黏膜中黏附连接标记物(β-连环蛋白和 E-钙黏蛋白)和紧密连接标记物(闭合蛋白-1 和紧密连接蛋白-1)的表达。
黏附连接和紧密连接标记蛋白在口腔黏膜的生发层和功能层中均迅速且一致地上调。这代表了对临床相关分割照射方案上皮辐射反应的一个以前未知的参数。
分割照射显著增强了所有研究蛋白的表达。本研究揭示了上皮对分割照射的辐射反应的一个新参数。