Radioprotectors, Radiomitigators, and Radiosensitizers

Abstract

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.

Kinetics of Metallofullerenol Reactions with the Products of Water Radiolysis: Implications for Radiotherapeutics

“…The protection of healthy tissues against the damaging effects of ionizing radiation is a crucial aspect of radiotherapy. However, currently available chemicals for either the prevention, mitigation, or treatment of injuries arising from ionizing radiation exposure are very limited. , For instance, amifostine, a commonly used radioprotectant in clinical settings, requires relatively high doses for effectiveness. While it acts by locally scavenging highly reactive radicals, amifostine proves ineffective against some less reactive secondary radiochemical products .…”

“…Other drugs function as radiomitigators, aiding in the reduction and repair of damage through various modes of action. These modes include the restoration of tissue by stimulating cell proliferation (e.g., G-CSF analogs like filgrastim), indirect antioxidant action by triggering the expression of antioxidant and gene repair enzymes (e.g., entolimod), chelation of radionuclides and transition metals responsible for Fenton-type reactions (e.g., metformin or DTPA), prevention of chromosomal damage during mitosis by halting cell division (e.g., genistein), or stimulation of prosurvival signaling pathways that lead to DNA repair rather than apoptosis (e.g., recilisib). ,, …”