Identification of Potential ProphylacticMedical Countermeasures Against Acute Radiation Syndrome (ARS)

Authors

• Kia T. Liermann-Wooldrik, University of Nebraska Medical Center
• Arpita Chatterjee, University of Nebraska Medical CenterFollow
• Elizabeth A. Kosmacek, University of Nebraska Medical Center
• Molly S. Myers, University of Nebraska Medical Center
• Oluwaseun Adebisi, University of Nebraska Medical Center
• Louise Monga-Wells, University of Nebraska Medical CenterFollow
• Liu Mei, University of Nebraska Medical Center
• Michelle P. Takacs, University of Nebraska-Lincoln
• Patrick H. Dussault, University of Nebraska-LincolnFollow
• Daniel R. Draney, University of Nebraska-Lincoln
• Robert Powers, University of Nebraska-Lincoln
• James W. Checco, University of Nebraska-LincolnFollow
• Chittibabu Guda, University of Nebraska Medical CenterFollow
• Tomáš Helikar, University of Nebraska-Lincoln
• David B. Berkowitz, University of Nebraska-linFollow
• Kenneth W. Bayles, University of Nebraska Medical Center
• Alan H. Epstein, Defense Health AgencyFollow
• Lynnette Cary, Uniformed Services University of the Health Sciences
• Daryl J. Murry, University of Nebraska Medical Center
• Rebecca E. Oberley-Deegan, University of Nebraska Medical CenterFollow

ORCID IDs

Liermann-Wooldrik https://orcid.org/0009-0002-3070-2743

Powers https://orcid.org/0000-0001-9948-6837

Checco https://orcid.org/0000-0003-1165-6163

Guda https://orcid.org/0000-0002-5393-9316

Berkowitz https://orcid.org/0000-0001-7550-0112

Murry https://orcid.org/0000-0002-4169-5027

Oberley-Deegan https://orcid.org/0000-0002-0391-142X

Document Type

Article

Date of this Version

2025

Citation

International Journal of Molecular Sciences (2025) 26: 4055

doi: 10.3390/ijms26094055

Comments

Open access

License: CC BY 4.0

Abstract

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 Mus musculus 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.