Models for Evaluating Agents Intended for the Prophylaxis, Mitigation and Treatment of Radiation Injuries Report of an NCI Workshop, December 3–4, 2003

Abstract

To develop approaches to prophylaxis/protection, mitigation and treatment of radiation injuries, appropriate models are needed that integrate the complex events that occur in the radiation-exposed organism. While the spectrum of agents in clinical use or preclinical development is limited, new research findings promise improvements in survival after whole-body irradiation and reductions in the risk of adverse effects of radiotherapy. Approaches include agents that act on the initial radiochemical events, agents that prevent or reduce progression of radiation damage, and agents that facilitate recovery from radiation injuries. While the mechanisms of action for most of the agents with known efficacy are yet to be fully determined, many seem to be operating at the tissue, organ or whole animal level as well as the cellular level. Thus research on prophylaxis/protection, mitigation and treatment of radiation injuries will require studies in whole animal models. Discovery, development and delivery of effective radiation modulators will also require collaboration among researchers in diverse fields such as radiation biology, inflammation, physiology, toxicology, immunology, tissue injury, drug development and radiation oncology. Additional investment in training more scientists in radiation biology and in the research portfolio addressing radiological and nuclear terrorism would benefit the general population in case of a radiological terrorism event or a large-scale accidental event as well as benefit patients treated with radiation.

Radiation as a Risk Factor for Cardiovascular Disease

“…Health have recommended terminology for such therapies that is consistent with other areas of medicine: prophylactic agents/protectors are agents that must be given before radiation exposure; mitigators are agents that are given after exposure, but before the appearance of overt evidence of injury; and treatment refers to agents that are given after overt symptoms develop (84). Agents with evidence for cardiac efficacy include free radical scavengers, antioxidants, statins, steroids, natural products, and other agents (8,10,36,80,90).…”

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures

“…The harmful effects of radiation exposure on hematopoiesis have been well-established and studies conducted in various animal models have been valuable (Dainiak 2002;Waselenko et al 2004;Stone et al 2004;Augustine et al 2005;Williams et al 2010). Various animal models have been used to develop radiation countermeasures for H-ARS and the three models that have been used extensively in the majority of studies are mice, canines, and non-human primates (NHP) (Stone et al 2004;Augustine et al 2005;Dumont et al 2010).…”

“…Radiation countermeasures have been categorized into three classes based on the time of administration in relation to radiation exposure (Stone et al 2004): radioprotectors, radiomitigators, and radiation therapeutics. Radioprotectors (prophylaxis agents) are administered prior to radiation exposure to prevent radiation injury to tissue during the early phase of radiochemical events.…”

Antagonists of growth hormone releasing hormone (GHRH) given before whole body radiation lead to modulation of radiation response and organ-specific changes in the expression of angiogenesis

“…Whole body radiation from nuclear accidents can lead to acute radiation syndromes, involving the central nervous system, hematopoietic system, and gastrointestinal tract [1][2][3]. Whole body radiation can also be given therapeutically before transplantation.…”