New Approaches to Radiation Protection

Abstract

Radioprotectors are compounds that protect against radiation injury when given prior to radiation exposure. Mitigators can protect against radiation injury when given after exposure but before symptoms appear. Radioprotectors and mitigators can potentially improve the outcomes of radiotherapy for cancer treatment by allowing higher doses of radiation and/or reduced damage to normal tissues. Such compounds can also potentially counteract the effects of accidental exposure to radiation or deliberate exposure (e.g., nuclear reactor meltdown, dirty bomb, or nuclear bomb explosion); hence they are called radiation countermeasures. Here, we will review the general principles of radiation injury and protection and describe selected examples of radioprotectors/mitigators ranging from small-molecules to proteins to cell-based treatments. We will emphasize agents that are in more advanced stages of development.

Research and Development of Radioprotective Agents: A Mini-Review

“…Clinically, RAs should potentially protect patients during treatment and prevent the detrimental effects of radiation in order to provide therapeutic benefit and improve overall quality of life [3] . RAs could potentially counteract radiation effects from accidental or deliberate exposure hence they are also called radiation counter-measures [4] . The term of RA together with radioprotection was first introduced by Dale in 1942 during his studies on enzymes as indicative molecules [5] .…”

Radiation Induced Xerostomia: Current Concepts and Future Trends

“…ATM signaling also synchronises cell cycle check points like S and G2M, which would give adequate time for cells to repair and not to let pass the damages to daughter cells. Further, ATM also activates cell survival pathways like NF-kB signalling 15 .Base lesions are rectified by base excision repair pathways that use DNA polymerases and ligases. Other mechanisms attributed for acinar cell death though with less clarity are (i) de-granulation of secretory granules, (ii) impairment in aquaporin water channels, (iii) calcium signaling mechanisms, and (iv) loss of stem/progenitor cells 13 .…”

“…Intestinal cell mitogens (R-spondin1; 29 kDa, 263 amino acid protein) have been reported to stimulate ISC and undo gastrointestinal radiation features through Wnt/β-catenin pathway. Certain antibiotics (tetracycline) and anti-hypertensives (captopril) have also been reported radioprotective, though with less ambiguity in its mechanism 15 . Considering the complex nature of radiation damages in terms of the multiple systems it affects and the numerous response mechanisms it initiates, future applications may warrant use of novel formulations of chemical and biologic radioprotectors in combinations for effective radiation reversal in salivary glands.…”

Emerging Strategies in Radiation Countermeasure Research

“…Amifostine undergoes de-phosphorylation by alkaline phosphatase and becomes an active sulfhydryl compound (WR 1065); with easy cell permeability for free radical scavenging. Since alkaline phosphatase is less expressed in tumor cells, risk of tumor protection was not there [12,13]. Even though it went to phase III trials in reversing mucositis, xerostomia, dysphagia, pneumonitis and dermatitis, its side effects such as nausea, vomiting, hypotension and neurotoxicity outweighed the benefits and therefore is now not being used as a radioprotector [14].…”