title: Efficacy of radiation countermeasures depends on radiation quality.
abstract: The detonation of a nuclear weapon or a nuclear accident represent possible events with significant exposure to mixed neutron/γ-radiation fields. Although radiation countermeasures generally have been studied in subjects exposed to pure photons (γ or X rays), the mechanisms of injury of these low linear energy transfer (LET) radiations are different from those of high-LET radiation such as neutrons, and these differences may affect countermeasure efficacy. We compared 30-day survival in mice after varying doses of pure γ and mixed neutron/γ (mixed field) radiation (MF, Dn/Dt = 0.65), and also examined peripheral blood cells, bone marrow cell reconstitution, and cytokine expression. Mixed-field-irradiated mice displayed prolonged defects in T-cell populations compared to mice irradiated with pure γ photons. In mouse survival assays, the growth factor granulocyte colony-stimulating factor (G-CSF) was effective as a (post-irradiation) mitigator against both γ-photons and mixed-field radiation, while the thrombopoietin (TPO) mimetic ALXN4100TPO was effective only against γ irradiation. The results indicate that radiation countermeasures should be tested against radiation qualities appropriate for specific scenarios before inclusion in response plans.
authors.affiliation: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University, Bethesda, Maryland 20889-5603, USA.
authors.forename: Lynnette H
authors.initials: LH
authors.lastname: Cary
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Ngudiankama
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Salber
authors.forename: G David
authors.initials: GD
authors.lastname: Ledney
authors.forename: Mark H
authors.initials: MH
authors.lastname: Whitnall
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D001855:Bone Marrow Diseases / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D004353:Drug Evaluation, Preclinical; D000069585:Filgrastim; D005720:Gamma Rays / Q000009:adverse effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D018655:Lymphocyte Count; D051379:Mice; D009502:Neutrons / Q000009:adverse effects*; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000528:radiation effects; D013926:Thrombopoietin / Q000627:therapeutic use*
chemical_list: C559765:ALXN4100TPO; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin; D000069585:Filgrastim