Radiotherapy is commonly used for treating various types of cancer. In addition, adipose tissue is not routinely spared during typical radiation treatment. Although radiation is known to induce metabolic effects in patients, the effects of radiation therapy on adipose tissue have not been elucidated. Currently, few studies have investigated the impact of radiation exposure on adipose tissue, and these have primarily involved whole-body irradiation. This study aimed to understand the acutely persistent damage caused by clinically relevant radiation doses in adipocytes. Specifically, in vitro and in vivo, irradiated adipocytes increased reactive oxygen species (ROS) and lipid peroxidation levels and elevated lipolytic activity compared to unirradiated adipocytes. RNA sequencing also revealed the upregulation of senescence and inflammation pathways. We observed an increase in macrophage and T-cell accumulation at both 1 and 6 months after radiation exposure using in vivo models. Many of the changes observed in irradiated adipose tissue, including oxidative stress, metabolic dysfunction, inflammation, and senescence, are consistent with those observed in adipose tissue from obese patients, in which obesity is a known driver of many cancers. As adipose tissue damage is maintained chronically, protecting adipose tissue from the harmful effects of radiation exposure may improve radiation-induced toxicity and reduce cancer recurrence and progression.

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.