Liermann-Wooldrik Kia T, Chatterjee Arpita, Kosmacek Elizabeth A, Myers Molly S, Adebisi Oluwaseun, Monga-Wells Louise, Mei Liu, Takacs Michelle P, Dussault Patrick H, Draney Daniel R, Powers Robert, Checco James W, Guda Chittibabu, Helikar Tomáš, Berkowitz David B, Bayles Kenneth W, Epstein Alan H, Cary Lynnette, Murry Daryl J, Oberley-Deegan Rebecca E
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Int J Mol Sci. 2025 Apr 25;26(9):4055. doi: 10.3390/ijms26094055.
Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro with 4-8 Gy and in vivo by exposing to 7.3 Gy of whole-body irradiation. The primary endpoints of this study include cellular viability, DNA damage via γ-H2AX, colony formation, and overall survival at 30-days post-irradiation. In addition to evaluating the radioprotective performance of each compound, this study establishes a distinct set of in vitro assays to predict the overall efficacy of potential radioprotectors in an in vivo model of ARS. Furthermore, these results highlight the need for FDA-approved medical intervention to protect against ARS.
当造血细胞或胃肠道细胞因辐射暴露而受损，导致骨髓和胃肠道上皮干细胞群体的DNA损伤时，就会发生急性放射综合征（ARS）。在这些高度增殖的细胞类型中，DNA损伤会抑制干细胞的再增殖。在人类和动物中，这种无法再生干细胞的情况是致命的。在本手稿中，评估了几种化合物，氨磷汀、卡托普利、环丙沙星、PrC - 210、5 - AED（5 - 雄烯 - 3β，17β - 二醇）和5 - AET（5 - 雄烯 - 3β，7β，17β - 三醇）在体外和/或体内环境中预防ARS的能力。通过在体外以4 - 8 Gy照射小鼠骨髓细胞或大鼠肠上皮（IEC - 6）细胞，以及在体内以7.3 Gy进行全身照射来诱导ARS。本研究的主要终点包括细胞活力、通过γ - H2AX检测的DNA损伤、集落形成以及照射后30天的总体存活率。除了评估每种化合物的辐射防护性能外，本研究还建立了一套独特的体外试验，以预测潜在辐射防护剂在ARS体内模型中的总体疗效。此外，这些结果凸显了需要获得美国食品药品监督管理局（FDA）批准的医疗干预措施来预防ARS。
