Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Biomed Pharmacother. 2018 Oct;106:610-617. doi: 10.1016/j.biopha.2018.06.150. Epub 2018 Jul 11.
Radiation countermeasures are radioprotective agents that reduce the harmful effects of ionizing radiation. They have wide range of applications extending from protection of normal tissues of cancer patients during radiotherapy to safeguard people aftermath of radiologic or nuclear accidents. Despite the screening of thousands of natural and synthetic compounds, only few found place in clinic with limited tolerance. Therefore, mechanistic understanding is essential in the development of more suitable and customized radiation countermeasure agents. This review focuses on the mechanisms of radioprotection imparted by these agents. Radioprotectors are diverse and act through widely varying mechanisms that can be classified in 10 categories: 1) scavenging of free radicals; 2) enhancing DNA repair; 3) synchronizing of cells; 4) modulating redox sensitive genes; 5) modulating growth factors and cytokines; 6) inhibiting apoptosis; 7) repurposing of drug; 8) interacting and chelating of radionuclides; and therapeutic methods of tissue regeneration such as 9) gene therapy; and 10) stem cell therapy. The most common mechanism of radioprotection is the scavenging of free radicals whereas, modulation of growth factors, cytokines and redox genes emerge as effective strategies. Gene and stem cell therapies as therapeutic radiation countermeasures are being developed and can be applied in the near future to minimize the side effects of radiation exposure through tissues regenerations. Thus, the management of radiation exposure may require a holistic multi-mechanistic approaches to achieve optimal radiation protection during radiotherapy of cancer patients and in cases of nuclear eventualities.
辐射防护剂是减少电离辐射有害影响的放射防护剂。它们的应用范围很广，从保护癌症患者放疗期间的正常组织，到保护放射性或核事故后的人员。尽管对数千种天然和合成化合物进行了筛选，但只有少数几种在临床上具有有限的耐受性。因此，在开发更合适和定制的辐射防护剂时，对机制的理解是必不可少的。本综述重点介绍了这些试剂所赋予的辐射防护机制。辐射防护剂种类繁多，作用机制广泛，可分为 10 类：1）清除自由基；2）增强 DNA 修复；3）细胞同步化；4）调节氧化还原敏感基因；5）调节生长因子和细胞因子；6）抑制细胞凋亡；7）药物再利用；8）放射性核素的相互作用和螯合；9）组织再生的治疗方法，如基因治疗；和 10）干细胞治疗。最常见的辐射防护机制是清除自由基，而生长因子、细胞因子和氧化还原基因的调节则成为有效的策略。基因和干细胞治疗作为治疗性辐射防护剂正在开发中，并可在不久的将来应用于通过组织再生来最小化辐射暴露的副作用。因此，辐射管理可能需要采用整体的多机制方法，以在癌症患者的放疗和核事故中实现最佳的辐射防护。
