Radioprotection and Radiomitigation: From the Bench to Clinical Practice.

Autores de IIS La Fe

• Juan Ignacio Villaescusa Blanca

  Autor

• José Miguel Soriano Del Castillo

  Autor

• Alegría Montoro Pastor

  Autor

Participantes ajenos a IIS La Fe

• Obrador E
• Salvador R
• Estrela JM

Grupos

• Investigacion Biomédica en Imagen (GIBI 2-30)

  Investigador Principal

  Leonor Cerdá Alberich

• Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética clínica

  Leader

  Juan Francisco Merino Torres

Abstract

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.

Keywords

• antioxidants, free radicals, ionizing radiations, radiomitigators, radioprotectors