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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / therapeutic use*
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Antibodies, Monoclonal, Humanized
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Bone Marrow / drug effects
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Bone Marrow / pathology
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Bone Marrow / radiation effects
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Bone Marrow Diseases / blood
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Bone Marrow Diseases / etiology
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Bone Marrow Diseases / immunology
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Bone Marrow Diseases / prevention & control*
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Cytokines / blood
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Drug Evaluation, Preclinical
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Filgrastim
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Gamma Rays / adverse effects*
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Granulocyte Colony-Stimulating Factor / therapeutic use*
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Hematopoiesis / drug effects
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Hematopoiesis / radiation effects
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / pathology
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Hematopoietic Stem Cells / radiation effects
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Lymphocyte Count
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Mice
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Neutrons / adverse effects*
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Radiation Injuries, Experimental / blood
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Radiation Injuries, Experimental / etiology
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Radiation Injuries, Experimental / immunology
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Radiation Injuries, Experimental / prevention & control*
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Radiation-Protective Agents / therapeutic use*
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Recombinant Proteins / therapeutic use
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Spleen / drug effects
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Spleen / pathology
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Spleen / radiation effects
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T-Lymphocytes / radiation effects
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Thrombopoietin / therapeutic use*
Substances
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ALXN4100TPO
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Cytokines
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Radiation-Protective Agents
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Recombinant Proteins
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Granulocyte Colony-Stimulating Factor
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Thrombopoietin
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Filgrastim