Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan.
Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 754-8553, Japan.
Int J Mol Sci. 2024 Oct 19;25(20):11252. doi: 10.3390/ijms252011252.
The intestinal tract is a typical radiosensitive tissue, and radiation rectal injury is a severe side effect that limits the prescribed dose in radiotherapy of the abdominal and pelvic region. Understanding the post-irradiation kinetics of -positive stem cells is crucial in comprehending this adverse process. In this study, we utilized - knock-in mice expressing EGFP and LGR5 antibody fluorescence staining of wild-type mice. At the state of radiation injury, the qPCR analysis showed a significant decrease in the expression level of in the rectal epithelial tissue. The dose-response relationship analysis showed that at low to moderate doses up to 10 gray (Gy), -clustered populations were observed at the base of the crypt, whereas at sublethal doses (20 Gy and 29 Gy), the cells exhibited a dot-like scatter pattern, termed -dotted populations. During recovery, 30 days post-irradiation, -clustered populations gradually re-emerged while -dotted populations declined, implying that some of the -dotted stem cell populations re-clustered, aiding regenerations. Based on statistical analysis of the dose-response relationship using wild-type mice, the threshold dose for destroying these stem cell structures is 18 Gy. These findings may help set doses in mouse abdominal irradiation experiments for radiation intestinal injury and for understanding the histological process of injury development.
肠道是一种典型的辐射敏感组织,放射性直肠损伤是限制腹部和盆腔区域放射治疗规定剂量的严重副作用。了解阳性干细胞的辐射后动力学对于理解这一不良过程至关重要。在本研究中,我们利用表达 EGFP 和 LGR5 抗体荧光染色的阳性敲入小鼠和野生型小鼠。在辐射损伤状态下,qPCR 分析显示直肠上皮组织中表达水平显著下降。剂量反应关系分析表明,在低至中等剂量(高达 10 戈瑞(Gy))时,在隐窝底部观察到阳性簇集群体,而在亚致死剂量(20 Gy 和 29 Gy)时,细胞呈点状散射模式,称为阳性点状群体。在恢复期间,照射后 30 天,阳性簇集群体逐渐重新出现,而阳性点状群体减少,这表明一些阳性点状干细胞群体重新聚类,有助于再生。基于对野生型小鼠的剂量反应关系的统计分析,破坏这些干细胞结构的阈值剂量为 18 Gy。这些发现可能有助于确定小鼠腹部照射实验中辐射性肠损伤的剂量,并有助于理解损伤发展的组织学过程。