The Delayed Effects of Acute Radiation Exposure (DEARE): characteristics, mechanisms, animal models, and promising medical countermeasures.

There is an urgent demand for effective medical countermeasures (MCM) in the event of high-dose radiation exposure (prompt exposures of >2Gy (Coleman et al. 2015; Winters et al. 2023)) ranging from nuclear plant disasters to nuclear warfare. Less than 24 hours after exposure to high-dose ionizing radiation, victims develop a continuum of multi-system symptoms referred to as acute radiation syndrome (ARS). Survivors of ARS are at risk for developing the delayed effects of acute radiation exposure (DEARE), a spectrum of chronic illnesses involving multiple organ systems and occurring months to years after radiation exposure. The DEARE are believed to result from some combination of oxidative stress, inflammation, senescence, fibrosis, and loss of stem cell self-renewal potential in the ARS survivors (Robbins and Zhao 2004; Zhao and Robbins 2009; Chua et al. 2012; Unthank et al. 2015; Wang et al. 2016; Al-Jumayli et al. 2022). DEARE remain an understudied area of radiation injury, with most knowledge gleaned from observing atomic bomb survivors and post-radiotherapy cancer survivors.