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Terrorist use of nuclear weapons and radiation accidents put the human population at risk for exposure to life-threatening levels of radiation. Victims of lethal radiation exposure face potentially lethal acute injury, while survivors of the acute phase are plagued with chronic debilitating multi-organ injuries for years after exposure. Developing effective medical countermeasures (MCM) for the treatment of radiation exposure is an urgent need that relies heavily on studies conducted in reliable and well-characterized animal models according to the FDA Animal Rule. Although relevant animal models have been developed in several species and four MCM for treatment of the acute radiation syndrome are now FDA-approved, animal models for the delayed effects of acute radiation exposure (DEARE) have only recently been developed, and there are no licensed MCM for DEARE. Herein, we provide a review of the DEARE including key characteristics of the DEARE gleaned from human data as well as animal, mechanisms common to multi-organ DEARE, small and large animal models used to study the DEARE, and promising new or repurposed MCM under development for alleviation of the DEARE. Intensification of research efforts and support focused on better understanding of mechanisms and natural history of DEARE are urgently needed. Such knowledge provides the necessary first steps toward the design and development of MCM that effectively alleviate the life-debilitating consequences of the DEARE for the benefit of humankind worldwide.

The delayed effects of acute radiation exposure (DEARE): characteristics, mechanisms, animal models, and promising medical countermeasures