Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
Int J Radiat Biol. 2019 Nov;95(11):1447-1461. doi: 10.1080/09553002.2019.1644932. Epub 2019 Jul 30.
Incidents, such as nuclear facility accidents and the release of a 'dirty bomb', might result in not only external irradiation of personnel, but additional internal exposures through concomitant inhalation and/or ingestion of radioactive particulates. The purpose of this study was to define the impact of such a combination of radiation injuries on the hematopoietic niche. To assess changes in the murine hematopoietic system, we used a combined exposure of total body irradiation (TBI, 6 Gy) followed immediately by an internal (intraperitoneal) administration of 100 Ci of soluble Cs. We then evaluated acute survival in combined versus single modality exposure groups, as well as assessing hematopoietic function at 12 and 26 week time points. Acutely, the combination of external and internal exposures led to an unexpected delay in excretion of Cs, increasing the absorbed dose in the combined exposure group and leading to mortality from an acute hematopoietic syndrome. At 12 weeks, all exposure paradigms resulted in decreased numbers of phenotypic hematopoietic stem cells (HSCs), particularly the short-term HSCs (ST-HSC); long-term HSCs (LT-HSC) were depleted only in the internal and combined exposure groups. At 26 weeks, there was significant anemia in both the TBI alone and combined exposure groups. There were decreased numbers in both the LT- and ST-HSCs and decreased functionality, as measured by competitive repopulation, was seen in all radiation groups, with the greatest effects seen in the internal and combined exposure groups. Our data indicate that a combined injury of sublethal external irradiation with internal contamination induces significant and persistent changes in the hematopoietic system, as may have been predicted from the literature and our own group's findings. However, a novel observation was that the combined exposure led to an alteration in the excretion kinetics of the internal contamination, increasing the acute effects beyond those anticipated. As a result, we believe that a combined exposure poses a unique challenge to the medical community during both the acute and, possibly, delayed recovery stages.
事件，如核设施事故和“脏弹”的释放，不仅可能导致人员外部照射，而且还可能通过同时吸入和/或摄入放射性颗粒而导致额外的内部暴露。本研究的目的是定义这种辐射损伤组合对造血龛的影响。为了评估小鼠造血系统的变化，我们使用全身照射（TBI，6Gy）与立即进行的内部（腹腔内）给予 100Ci 可溶性 Cs 的联合暴露来评估。然后，我们评估了联合与单一模式暴露组的急性存活率，以及在 12 和 26 周时间点评估造血功能。急性情况下，外部和内部暴露的联合导致 Cs 排泄的意外延迟，增加了联合暴露组的吸收剂量，并导致急性造血综合征的死亡。在 12 周时，所有暴露模式都导致表型造血干细胞（HSCs）数量减少，特别是短期 HSCs（ST-HSC）；仅在内部和联合暴露组中耗尽了长期 HSCs（LT-HSC）。在 26 周时，单独 TBI 和联合暴露组都出现明显贫血。LT-HSC 和 ST-HSC 的数量均减少，所有辐射组的竞争再定植功能均降低，内部和联合暴露组的影响最大。我们的数据表明，亚致死性外部照射与内部污染的联合损伤会导致造血系统发生显著且持久的变化，这可能是根据文献和我们自己的研究结果预测的。然而，一个新的观察结果是，联合暴露导致内部污染的排泄动力学发生改变，使急性效应超过预期。因此，我们认为，在急性和可能的延迟恢复阶段，联合暴露对医疗界构成了独特的挑战。
