Department of Environmental Health Sciences, Eye Radiation and Environmental Research Laboratory, Columbia University, Mailman School of Public Health, 722 West 168th St., 11th Floor, New York, NY 10032, USA.
Division of Biological Stress Response, Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands.
Life Sci Space Res (Amst). 2017 Nov;15:43-54. doi: 10.1016/j.lssr.2017.07.005. Epub 2017 Jul 18.
World events, including the threat of radiological terrorism and the fear of nuclear accidents, have highlighted an urgent need to develop medical countermeasures to prevent or reduce radiation injury. Similarly, plans for manned spaceflight to a near-Earth asteroid or journey to Mars raise serious concerns about long-term effects of space radiation on human health and the availability of suitable therapeutic interventions. At the same time, the need to protect normal tissue from the deleterious effects of radiotherapy has driven considerable research into the design of effective radioprotectors. For more than 70 years, animal models of radiation cataract have been utilized to test the short and long-term efficacy of various radiation countermeasures. While some compounds, most notably the Walter Reed (WR) class of radioprotectors, have reported limited effectiveness when given before exposure to low-LET radiation, the human toxicity of these molecules at effective doses limits their usefulness. Furthermore, while there has been considerable testing of eye responses to X- and gamma irradiation, there is limited information about using such models to limit the injurious effects of heavy ions and neutrons on eye tissue. A new class of radioprotector molecules, including the sulfhydryl compound PrC-210, are reported to be effective at much lower doses and with far less side effects. Their ability to modify ocular radiation damage has not yet been examined. The ability to non-invasively measure sensitive, radiation-induced ocular changes over long periods of time makes eye models an attractive option to test the radioprotective and radiation mitigating abilities of new novel compounds.
世界事件,包括放射性恐怖主义的威胁和对核事故的恐惧,凸显了开发医学对策以预防或减少辐射损伤的迫切需要。同样,计划进行载人近地小行星飞行或前往火星的飞行,引发了对空间辐射对人类健康的长期影响以及是否有合适的治疗干预措施的严重关注。与此同时,需要保护正常组织免受放射治疗的有害影响,这促使人们对有效辐射防护剂的设计进行了大量研究。70 多年来,辐射性白内障的动物模型一直被用于测试各种辐射对策的短期和长期效果。虽然有些化合物,尤其是 Walter Reed(WR)类辐射防护剂,在暴露于低 LET 辐射之前给予时报告了有限的有效性,但这些分子在有效剂量下的人体毒性限制了它们的用途。此外,虽然已经对 X 射线和伽马射线照射的眼部反应进行了大量测试,但关于使用这些模型来限制重离子和中子对眼部组织的有害影响的信息有限。一类新的辐射防护剂分子,包括巯基化合物 PrC-210,据报道在低得多的剂量下有效,副作用也小得多。它们对眼部辐射损伤的修饰能力尚未得到检验。能够非侵入性地长时间测量敏感的辐射诱导的眼部变化,使得眼部模型成为测试新化合物的辐射防护和辐射缓解能力的一个有吸引力的选择。