title: Use of biomarkers for assessing radiation injury and efficacy of countermeasures.
abstract: Several candidate drugs for acute radiation syndrome (ARS) have been identified that have low toxicity and significant radioprotective and radiomitigative efficacy. Inasmuch as exposing healthy human volunteers to injurious levels of radiation is unethical, development and approval of new radiation countermeasures for ARS are therefore presently based on animal studies and Phase I safety study in healthy volunteers. The Animal Efficacy Rule, which underlies the Food and Drug Administration approval pathway, requires a sound understanding of the mechanisms of injury, drug efficacy, and efficacy biomarkers. In this context, it is important to identify biomarkers for radiation injury and drug efficacy that can extrapolate animal efficacy results, and can be used to convert drug doses deduced from animal studies to those that can be efficacious when used in humans. Here, we summarize the progress of studies to identify candidate biomarkers for the extent of radiation injury and for evaluation of countermeasure efficacy.
authors.affiliation: a F. Edward Hébert School of Medicine 'America's Medical School' , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.|b Armed Forces Radiobiology Research Institute , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
authors.affiliation: a F. Edward Hébert School of Medicine 'America's Medical School' , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.|b Armed Forces Radiobiology Research Institute , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Newman
authors.affiliation: a F. Edward Hébert School of Medicine 'America's Medical School' , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.|b Armed Forces Radiobiology Research Institute , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
authors.forename: Patricia Lp
authors.initials: PL
authors.lastname: Romaine
authors.affiliation: c Departments of Pharmaceutical Sciences, Surgery, and Pathology , University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare Systems , Little Rock , AR , USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.affiliation: a F. Edward Hébert School of Medicine 'America's Medical School' , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
authors.forename: Harvey B
authors.initials: HB
authors.lastname: Pollard
mesh_terms: D054508:Acute Radiation Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015415:Biomarkers; D011837:Radiation-Protective Agents
keywords: Acute radiation syndrome; Animal Efficacy Rule; biomarkers; chromosomal aberration; irradiation; metabolomics; microRNA; radiation countermeasures