The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential radioprotectors. Early development of such agents focused on thiol synthetic compounds, e.g., amifostine (2-(3-aminopropylamino) ethylsulfanylphosphonic acid), approved as a radioprotector by the Food and Drug Administration (FDA, USA) but for limited clinical indications and not for nonclinical uses. To date, no new chemical entity has been approved by the FDA as a radiation countermeasure for acute radiation syndrome (ARS). All FDA-approved radiation countermeasures (filgrastim, a recombinant DNA form of the naturally occurring granulocyte colony-stimulating factor, G-CSF; pegfilgrastim, a PEGylated form of the recombinant human G-CSF; sargramostim, a recombinant granulocyte macrophage colony-stimulating factor, GM-CSF) are classified as radiomitigators. No radioprotector that can be administered prior to exposure has been approved for ARS. This differentiates radioprotectors (reduce direct damage caused by radiation) and radiomitigators (minimize toxicity even after radiation has been delivered). Molecules under development with the aim of reaching clinical practice and other nonclinical applications are discussed. Assays to evaluate the biological effects of ionizing radiations are also analyzed.

Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms.

Ionizing radiation has been a critical tool in various fields, such as medicine, agriculture, and energy production, since its discovery in 1895. While its applications—particularly in cancer treatment and diagnostics—offer significant benefits, ionizing radiation also poses risks due to its potential to cause molecular and cellular damage. This damage can occur through the direct ionization of biological macromolecules, such as deoxyribonucleic acid (DNA), or indirectly through the radiolysis of water, which generates reactive oxygen species (ROS) that further damage cellular components. Radioprotectors, compounds that protect against radiation-induced damage, have been extensively researched since World War II. These agents work by enhancing DNA repair, scavenging free radicals, and boosting antioxidant defenses, thereby protecting healthy tissues. Furthermore, some radioprotective agents also stimulate DNA repair mechanisms even after radiation exposure, aiding in recovery from radiation-induced damage. This article explores the molecular mechanisms of radiation-induced damage, focusing on both direct and indirect effects on DNA, and discusses the role of radioprotectors, their mechanisms of action, and recent advancements in the field. The findings underscore the importance of developing effective radioprotective strategies, particularly in medical and industrial settings, where radiation exposure is prevalent.

For millennia, naturopaths and physicians have used Ganoderma lucidum (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia. Indeed, a radioprotective effect has been reported in the isolated components of its extracts. A systematic review and meta-analyses (PRISMA) was conducted in March 2020, searching databases including PubMed, Scopus, Embase, and Google Scholar, along with Clinical Trials. The inclusion criteria were ex vivo, in vitro, and in vivo studies, with full texts in English, conducted to determine the radioprotective benefits of G. lucidum, or reports in which ionizing radiation was used. From a total number of 1109 records identified, 15 full text articles were eligible, none of them were clinical trials. In vivo studies reveal the efficiency of G. lucidum aqueous extracts of polysaccharides and triterpenes in mice exposed to γ-rays. In plasmid, they can reduce radiation damage as an increment of the open circular form, as well as increase the DNA extension, as shown in vitro studies. Ex vivo studies conducted in human blood cells show the radioprotective effect of β-glucan of aqueous extract of G. lucidum, nevertheless, its implementation as radioprotector to humans is in need of further clinical research studies.

The radioprotective effect ex vivo, in vitro and in vivo of vitamins was reviewed using PubMed and Embase and conducted according to the PRISMA statement. A total of 38 articles were included in this review, which includes the radioprotective effect of vitamins from ex vivo, in vitro and in vivo studies. Vitamins A, C, D and E were used alone, in combination or with other nutritional and non-nutritional compounds. The use of vitamins in natural form or supplementation can be useful to reduce the radiation effect in the body, organs and/or cells. Only four (A, C, D and E) out of thirteen vitamins have been detected with radioprotective properties being mainly vitamin E followed by vitamin C, A and D.

This chapter gives an overview of molecules and mechanisms able to intervene with the biological effects of ionizing radiation (IR), either related to their clinical use in radiotherapy or in the field of radiation protection in case of an accidental exposure to radiation and/or nuclear emergencies. According to the National Cancer Institute, “radiomodifiers” can be classified into (a) radioprotectors (protect molecules and tissues from direct and indirect damage induced by IR) or (b) radiomitigators (reduce and help to repair damage), depending on whether they are administered pre- or post-IR exposure, respectively. Most of them are free radical scavengers and antioxidants (or enhancers of the antioxidant defenses), increase DNA repair mechanisms, have anti-inflammatory properties, and/or prevent cell death. On the other hand, (c) radiosensitizers directly or indirectly enhance DNA damage and ROS production, increasing IR toxicity on tumor cells, thus they are used to increase radiotherapy efficacy in cancer patients. The section “Radionuclides and methods to treat contaminated individuals” describes the medical consequences and treatment modalities of internal contamination by radionuclides. Overall, the chapter discusses the effects of most currently known radiomodifiers, their specific properties, and their mechanisms of action, by emphasizing results obtained in recent preclinical and clinical trials.