title: Radiobiologic effects of GS-nitroxide (JP4-039) on the hematopoietic syndrome.
abstract: OBJECTIVE
  Total-body irradiation (TBI) doses in the range of 2-8 Gy are associated with a drop in peripheral blood counts, decreased bone marrow cellularity, and hematopoietic syndrome. Radiation mitigators must be safe for individuals likely to recover spontaneously.
  
  
  METHODS
  Female C57BL/6HNsd mice exposed to 9.0 and 9.15 Gy TBI, received intraperitoneal (10 mg/kg) JP4-039, a novel radiation mitigator, 24 hours after irradiation and were followed for hematopoietic recovery.
  
  
  RESULTS
  Irradiated mice showed reduced peripheral blood lymphocytes and neutrophils and bone marrow cellularity at day 5. Serum electrolytes, liver and renal function tests showed no deleterious effect of JP4-039-after irradiation, and no reduction in survival compared to irradiated controls. Marrow recovery measured as cellularity, and hematopoietic colony-forming cells including primitive granulocyte-erythroid-megakaryocyte-monocytes (GEMM), reached pre-irradiation levels by day 30 in JP4-039 treated groups. Mice receiving single or multiple administrations of JP4-039 showed an early return of CFU-GEMM.
  
  
  CONCLUSIONS
  JP4-039 (GS-Nitroxide) is a safe radiation mitigator in mice warranting studies in larger animals and potentially a Phase I Clinical Trial.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Julie P
authors.initials: JP
authors.lastname: Goff
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.forename: Tracy
authors.initials: T
authors.lastname: Dixon
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Darcy
authors.initials: D
authors.lastname: Franicola
authors.forename: Donna
authors.initials: D
authors.lastname: Shields
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001773:Blood Cells / Q000187:drug effects / Q000528:radiation effects; D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009589:Nitrogen Oxides / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D016019:Survival Analysis; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects* / Q000401:mortality
chemical_list: C544775:JP4-039; D009589:Nitrogen Oxides; D011837:Radiation-Protective Agents