Efficacy of Radiation Countermeasures Depends on Radiation Quality

• Published in: Radiation research 2012-05, Vol.177 (5), p.663-675
• Main Authors: Cary, Lynnette H., Ngudiankama, Barbara F., Salber, Rudolph E., Ledney, G. David, Whitnall, Mark H.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Blood; Bone marrow; Bone Marrow - drug effects; Bone Marrow - pathology; Bone Marrow - radiation effects; Bone Marrow Diseases - blood; Bone Marrow Diseases - etiology; Bone Marrow Diseases - immunology; Bone Marrow Diseases - prevention & control; Countermeasures; Cytokines; Cytokines - blood; Drug Evaluation, Preclinical; Effectiveness; Filgrastim; Gamma Rays - adverse effects; Granulocyte Colony-Stimulating Factor - therapeutic use; Hematopoiesis - drug effects; Hematopoiesis - radiation effects; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - pathology; Hematopoietic Stem Cells - radiation effects; Inclusions; Irradiation; Lymphocyte Count; Mice; Military technology; Neutrons; Neutrons - adverse effects; Neutrophils; Photons; Radiation dosage; Radiation Injuries, Experimental - blood; Radiation Injuries, Experimental - etiology; Radiation Injuries, Experimental - immunology; Radiation Injuries, Experimental - prevention & control; Radiation-Protective Agents - therapeutic use; Recombinant Proteins - therapeutic use; REGULAR ARTICLES; Space life sciences; Spleen - drug effects; Spleen - pathology; Spleen - radiation effects; Stem cells; Survival; T-Lymphocytes - radiation effects; Thrombopoietin - therapeutic use
• ISSN: 0033-7587; 1938-5404
• DOI: 10.1667/RR2783.1

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.