Identification of Potential Prophylactic Medical Countermeasures Against Acute Radiation Syndrome (ARS)
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 <i>Mus musculus</i> 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.
Authors
- Kenneth W. Bayles (ORCID: https://orcid.org/0000-0001-9521-3540)
- James W. Checco (ORCID: https://orcid.org/0000-0003-1165-6163)
- Arpita Chatterjee (ORCID: https://orcid.org/0000-0001-8959-2353)
- Robert Powers (ORCID: https://orcid.org/0000-0001-9948-6837)
- Elizabeth A. Kosmacek (ORCID: https://orcid.org/0000-0002-0169-5612)
- David B. Berkowitz (ORCID: https://orcid.org/0000-0001-7550-0112)
- Patrick H. Dussault (ORCID: https://orcid.org/0000-0002-9834-1350)
- Lynnette Cary (ORCID: https://orcid.org/0000-0001-5548-9489)
- Chittibabu Guda (ORCID: https://orcid.org/0000-0002-5393-9316)
- Oluwaseun Abraham Adebisi (ORCID: https://orcid.org/0000-0003-4380-7923)
- Molly Myers (ORCID: https://orcid.org/0000-0001-7943-2268)
- Rebecca E. Oberley‐Deegan (ORCID: https://orcid.org/0000-0002-0391-142X)
- Tomáš Helikar (ORCID: https://orcid.org/0000-0003-3653-1906)
- Daryl J. Murry (ORCID: https://orcid.org/0000-0002-4169-5027)
- Kia T. Liermann-Wooldrik (ORCID: https://orcid.org/0009-0002-3070-2743)
- Mei Liu (ORCID: https://orcid.org/0000-0002-1090-7672)
- Alan H. Epstein
- Mária Takács
- Daniel R. Draney
- Louise Monga-Wells
Institutions
- University of Nebraska–Lincoln (US)
- Uniformed Services University of the Health Sciences (US)
- Defense Health Agency (US)
- University of Nebraska Medical Center (US)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-04-25
- DOI
- https://doi.org/10.3390/ijms26094055
- Citations
- 4
- Primary Topic
- Effects of Radiation Exposure
- Type
- article
- Field-Weighted Citation Impact
- 5.44
Funders
- Wisconsin Alumni Research Foundation
- Nebraska Center for Integrated Biomolecular Communication