Schmidt Margret, Piro-Hussong Aline, Siegemund Annett, Gabriel Peggy, Dörr Wolfgang
Department of Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University Dresden, 01307, Dresden, Germany,
Radiat Environ Biophys. 2014 Nov;53(4):629-34. doi: 10.1007/s00411-014-0552-7. Epub 2014 Jun 15.
Early oral mucositis occurs in response to accidental upper partial body exposure as well as to radiotherapy in the head-and-neck region. This study was initiated to define the potential of mobilization of endogenous bone marrow (BM) stem cells by rHuG-CSF or of bone marrow transplantation (BMT) to reduce the effect of single-dose irradiation on mouse oral epithelium. A 3 × 3 mm(2) area of the lower tongue surface of mice was irradiated with graded single doses (day 0). Mucosal ulceration was used as the endpoint for dose-response analyses. Stem cells were mobilized by rHuG-CSF (8 times/4 days), timed to achieve a maximum of circulating stem cells on days 0, +1, +4, +8 or +10. Alternatively, syngeneic BM was transplanted on these days. The ED(50) (dose at which ulceration is expected in 50 % of the animals) for irradiation alone was 11.9 ± 3.4 Gy. Mobilization of stem cells with a maximum of circulating stem cells on days +4, +8 or +10 significantly increased the ED(50) to 25.5 ± 10.1, 23.5 ± 10.1 and 26.5 ± 13.0 Gy. In contrast, a maximum of circulating stem cells on day 0 or day +1 had no effect. BMT did not result in a significant change in isoeffective doses in any of the protocols. In conclusion, the response of oral mucosal epithelium to a single-radiation exposure can be significantly reduced by post-exposure mobilization, but not by transplantation, of BM stem cells.
早期口腔黏膜炎可因上半身意外局部暴露以及头颈部放疗而发生。开展本研究旨在确定重组人粒细胞集落刺激因子（rHuG-CSF）动员内源性骨髓（BM）干细胞或进行骨髓移植（BMT）以减轻单剂量照射对小鼠口腔上皮影响的可能性。对小鼠舌腹表面3×3 mm²区域进行分级单剂量照射（第0天）。将黏膜溃疡用作剂量反应分析的终点。通过rHuG-CSF（每4天8次）动员干细胞，使其在第0、+1、+4、+8或+10天达到循环干细胞数量最多。或者，在这些日子进行同基因BM移植。单纯照射的半数有效剂量（ED50，预计50%动物出现溃疡的剂量）为11.9±3.4 Gy。在第+4、+8或+10天使循环干细胞数量最多的干细胞动员显著将ED50提高至25.5±10.1、23.5±10.1和26.5±13.0 Gy。相比之下，在第0天或+1天循环干细胞数量最多则没有效果。在任何方案中，BMT均未导致等效应剂量发生显著变化。总之，暴露后动员BM干细胞可显著降低口腔黏膜上皮对单次辐射暴露的反应，但移植则不能。
