title: Beta androstenediol mitigates the damage of 1 GeV/n Fe ion particle radiation to the hematopoietic system.
abstract: Space exploration is associated with exposure to 1-3 Gy solar particle radiation and galactic cosmic radiation that could increase cancer rates. Effective nontoxic countermeasures to high linear energy transfer (LET) radiation exposure are highly desirable but currently not available. The aim was to determine whether a single subcutaneous injection of androstenediol (Δ(5) androsten-3β, 17β-diol [AED]) could mitigate and restore the mouse hematopoetic system from the radiation-mediated injury of 3 Gy whole-body high LET (56)Fe(26+) exposure. The findings show that postradiation AED treatment has an overall positive and significant beneficial effect to restore the levels of hematopoeitic elements (p<0.001). Androstenediol treatment significantly increased monocyte levels at days 4, 7, and 14 and, similarly, increased red blood cell, hemoglobin, and platelet counts. Flow cytometry analysis 14 days after radiation and AED treatment demonstrated an increase (p<0.05) in bone marrow cells counts. Ex vivo osteoclastogenesis studies show that AED treatment is necessary and advantageous for the development and restoration of osteoclastogenesis after radiation exposure. These findings clearly show that androstenediol functions as a countermeasure to remedy hematopoeitic injury mediated by high LET iron ion radiation. Presently, no other agent has been shown to have such properties.
authors.affiliation: Department of Microbiology, Immunology, Virginia Commonwealth University, 1101 E. Marshal Street, Richmond, VA 23298-0678, USA. loria@vcu.edu
authors.forename: Roger
authors.initials: R
authors.lastname: Loria
authors.forename: Mathew
authors.initials: M
authors.lastname: Beckman
authors.forename: Daniel
authors.initials: D
authors.lastname: Contaifer
authors.forename: Francisco
authors.initials: F
authors.lastname: Tamariz
authors.forename: David
authors.initials: D
authors.lastname: Gibb
authors.forename: Laura
authors.initials: L
authors.lastname: Thompson
authors.forename: Peter
authors.initials: P
authors.lastname: Guida
mesh_terms: D015114:Androstenediol / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D020450:Heavy Ions / Q000009:adverse effects*; D006413:Hematopoietic System / Q000187:drug effects* / Q000528:radiation effects*; D007279:Injections, Subcutaneous; D007501:Iron / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014916:Whole-Body Irradiation
chemical_list: D011837:Radiation-Protective Agents; D015114:Androstenediol; D007501:Iron