Kurpinski Kyle, Jang Deok-Jin, Bhattacharya Sanchita, Rydberg Bjorn, Chu Julia, So Joanna, Wyrobek Andy, Li Song, Wang Daojing
Department of Bioengineering, University of California-Berkeley, Berkeley, CA, USA.
Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):869-77. doi: 10.1016/j.ijrobp.2008.10.002. Epub 2008 Dec 26.
Stem cells hold great potential for regenerative medicine, but they have also been implicated in cancer and aging. How different kinds of ionizing radiation affect stem cell biology remains unexplored. This study was designed to compare the biological effects of X-rays and of high-linear energy transfer (LET) (56)Fe ions on human mesenchymal stem cells (hMSC).
A multi-functional comparison was carried out to investigate the differential effects of X-rays and (56)Fe ions on hMSC. The end points included modulation of key markers such as p53, cell cycle progression, osteogenic differentiation, and pathway and networks through transcriptomic profiling and bioinformatics analysis.
X-rays and (56)Fe ions differentially inhibited the cell cycle progression of hMSC in a p53-dependent manner without impairing their in vitro osteogenic differentiation process. Pathway and network analyses revealed that cytoskeleton and receptor signaling were uniquely enriched for low-dose (0.1 Gy) X-rays. In contrast, DNA/RNA metabolism and cell cycle regulation were enriched for high-dose (1 Gy) X-rays and (56)Fe ions, with more significant effects from (56)Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA binding/transferase activity were perturbed more severely by 1 Gy (56)Fe ions than by 1 Gy X-rays, consistent with the significant G2/M arrest for the former while not for the latter.
(56)Fe ions exert more significant effects on hMSC than X-rays. Since hMSC are the progenitors of osteoblasts in vivo, this study provides new mechanistic understandings of the relative health risks associated with low- and high-dose X-rays and high-LET space radiation.
干细胞在再生医学中具有巨大潜力，但它们也与癌症和衰老有关。不同类型的电离辐射如何影响干细胞生物学仍未得到探索。本研究旨在比较X射线和高传能线密度（LET）的（56）Fe离子对人间充质干细胞（hMSC）的生物学效应。
进行了一项多功能比较，以研究X射线和（56）Fe离子对hMSC的不同影响。终点包括通过转录组分析和生物信息学分析对关键标志物如p53的调节、细胞周期进程、成骨分化以及途径和网络。
X射线和（56）Fe离子以p53依赖的方式不同程度地抑制了hMSC的细胞周期进程，而不损害其体外成骨分化过程。途径和网络分析表明，细胞骨架和受体信号在低剂量（0.1 Gy）X射线作用下独特地富集。相比之下，DNA/RNA代谢和细胞周期调节在高剂量（1 Gy）X射线和（56）Fe离子作用下富集，其中（56）Fe离子的影响更显著。具体而言，1 Gy的（56）Fe离子比1 Gy的X射线更严重地干扰了DNA复制、DNA链延伸和DNA结合/转移酶活性，这与前者导致显著的G2/M期阻滞而后者没有一致。
（56）Fe离子对hMSC的影响比X射线更显著。由于hMSC是体内成骨细胞的祖细胞，本研究为低剂量和高剂量X射线以及高LET空间辐射相关的相对健康风险提供了新的机制理解。
