title: Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis.
abstract: OBJECTIVE
  Amifostine is a highly efficacious cytoprotectant when administered in vivo at high doses. However, at elevated doses, drug toxicity manifests for general, non-clinical radioprotective purposes. Various strategies have been developed to avoid toxic side-effects: The simplest is reducing the dose. In terms of protecting hematopoietic tissues, where does this effective, non-toxic minimum dose lie?
  
  
  METHODS
  C3H/HEN mice were administered varying doses of amifostine (25-100 mg/kg) 30 min prior to cobalt-60 irradiation and euthanized between 4-14 days for blood and bone marrow collection and analyses.
  
  
  RESULTS
  Under steady-state, amifostine had little effect on bipotential and multi-potential marrow progenitors but marginally suppressed a more primitive, lineage negative progenitor subpopulation. In irradiated animals, prophylactic drug doses greater than 50 mg/kg resulted in significant regeneration of bipotential progenitors, moderate regeneration of multipotential progenitors, but no significant and consistent regeneration of more primitive progenitors. The low amifostine dose (25 mg/kg) failed to elicit consistent and positive, radioprotective actions on any of the progenitor subtypes.
  
  
  CONCLUSIONS
  Radioprotective doses for amifostine appear to lie between 25 and 50 mg/kg. Mature, lineage-restricted progenitors appear to be more responsive to the protective effects of low doses of amifostine than the more primitive, multipotential progenitors.
authors.affiliation: Tech Micro Services , Bethesda, MD , USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Seed
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Inal
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*
chemical_list: D011837:Radiation-Protective Agents; D019009:Proto-Oncogene Proteins c-kit; D004999:Amifostine
keywords: Amifostine; WR2721; bone marrow; hematopoietic progenitors; radiation; radioprotectants