Booth Catherine, Tudor Gregory L, Katz Barry P, MacVittie Thomas J
*Epistem Ltd, Manchester, UK; †Indiana University, School of Medicine, Department of Biostatistics, Indianapolis, IN; ‡University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.
Health Phys. 2015 Nov;109(5):399-413. doi: 10.1097/HP.0000000000000356.
Long term or residual damage post-irradiation has been described for many tissues. In hematopoietic stem cells (HSC), this is only revealed when the HSC are stressed and required to regenerate and repopulate a myeloablated host. Such an assay cannot be used to assess the recovery potential of previously irradiated intestinal stem cells (ISC) due to their incompatibility with transplantation. The best approximation to the HSC assay is the crypt microcolony assay, also based on clonogen survival. In the current study, the regenerative capacity of intestinal clonogenic cells in mice that had survived 13 Gy irradiation (with 5% bone marrow shielding to allow survival through the hematopoietic syndrome) and were then aged for 200 d was compared to previously unirradiated age-matched controls. Interestingly, at 200 d following 13 Gy, there remained a statistically significant reduction in crypts present in the various small intestinal regions (illustrating that the gastrointestinal epithelium had not fully recovered despite the 200-d interval). However, upon re-irradiation on day 196, those mice previously irradiated had improved crypt survival and regeneration compared to the age-matched controls. This was evident in all regions of the small intestine following 11-13 Gy re-exposure. Thus, there were either more clonogens per crypt within those previously irradiated and/or those that were present were more radioresistant (possibly because a subpopulation was more quiescent). This is contrary to the popular belief that previously irradiated animals may have an impaired/delayed regenerative response and be more radiosensitive.
许多组织都有关于辐射后长期或残留损伤的描述。在造血干细胞（HSC）中，只有当HSC受到应激并需要再生和重新填充经清髓处理的宿主时，这种损伤才会显现出来。由于与移植不兼容，这样的检测方法不能用于评估先前受辐照的肠道干细胞（ISC）的恢复潜力。与HSC检测最接近的方法是隐窝微集落检测，它同样基于克隆原的存活情况。在本研究中，将存活于13 Gy辐照（5%骨髓屏蔽以使其在造血综合征中存活）后再老化200天的小鼠肠道克隆细胞的再生能力，与年龄匹配的未辐照对照小鼠进行了比较。有趣的是，在13 Gy辐照后200天，各个小肠区域的隐窝数量仍有统计学上的显著减少（说明尽管间隔了200天，胃肠道上皮仍未完全恢复）。然而，在第196天再次辐照时，那些先前受过辐照的小鼠与年龄匹配的对照相比，隐窝存活和再生情况有所改善。在再次接受11 - 13 Gy辐照后的小肠所有区域，这一点都很明显。因此，在那些先前受过辐照的小鼠中，要么每个隐窝中的克隆原更多，要么现存的克隆原更具放射抗性（可能是因为一个亚群更处于静止状态）。这与普遍认为的先前受过辐照的动物可能具有受损/延迟的再生反应且对辐射更敏感的观点相反。
