title: Protection against gamma-irradiation with 5-androstenediol.
abstract: We showed previously that treatment of gamma-irradiated female B6D2F1 mice with 5-androstenediol (AED) enhanced survival, stimulated myelopoiesis, and ameliorated radiation-induced decreases in circulating neutrophils and platelets. We have now tested survival in male CD2F1 mice, and we have investigated molecular and functional effects on neutrophils and bone marrow stromal cells and screened for toxicity in female B6D2F1 mice. AED (160 mg/kg, subcutaneously, 24 hours before irradiation) enhanced survival in male CD2F1 mice with a dose-reduction factor of 1.23, similar to the dose-reduction factor of 1.26 found previously for female B6D2F1 mice. Expression of CD11b, a developmental marker, was reduced on circulating neutrophils after either in vivo AED administration or whole-body gamma-irradiation (3 Gy), but neutrophil peroxidase activity was unchanged. Stromal cell progenitors (fibroblastoid colony-forming units) were reduced in marrow 5 days after AED injection in nonirradiated mice. Clinical chemistry, histopathology, and behavioral assays showed no evidence of toxicity. We conclude that AED and related steroids are attractive candidates to explore as countermeasures to high- and low-level ionizing radiation.
authors.affiliation: Radiation Casualty Management Team, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Whitnall
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Elliott
authors.forename: Michael R
authors.initials: MR
authors.lastname: Landauer
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Wilhelmsen
authors.forename: LuAnn
authors.initials: L
authors.lastname: McKinney
authors.forename: K Sree
authors.initials: KS
authors.lastname: Kumar
authors.forename: Venkataraman
authors.initials: V
authors.lastname: Srinivasan
authors.forename: G David
authors.initials: GD
authors.lastname: Ledney
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Seed
mesh_terms: D015114:Androstenediol / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005720:Gamma Rays; D008297:Male; D051379:Mice; D011837:Radiation-Protective Agents / Q000494:pharmacology*
chemical_list: D011837:Radiation-Protective Agents; D015114:Androstenediol