title: Improved hematopoiesis in GS-nitroxide (JP4-039)-treated mouse long-term bone marrow cultures and radioresistance of derived bone marrow stromal cell lines.
abstract: OBJECTIVE
  To determine if the small-molecule radioprotector GS-nitroxide, JP4-039, improved hematopoiesis in long-term bone marrow cultures (LTBMCs), explanted marrow from in vivo drug-treated C57BL/6NTac mice was maintained in JP4-039 for 25 weeks. Hematopoietic cell production and radiobiology of derived stromal cell lines was measured.
  
  
  METHODS
  Groups of LTBMCs were established from mouse groups. Stromal cell lines were established from the adherent layer of JP4-039-treated and untreated control groups.
  
  
  RESULTS
  LTBMCs maintained in JP4-039 exhibited increased production of total non-adherent and 7-day and 14-day hematopoietic colony-forming cells. Stromal cell lines derived from JP4-039-treated cultures were radioresistant in vitro, demonstrated a distinct squamous/epithelial morphology and overexpressed Nrf2, Ctgf, Lox, Tlr1, collagen 1a, Brd3, and Brd4.
  
  
  CONCLUSIONS
  Chronic treatment of bone marrow cultures and derived stromal cell lines with JP4-039 was non-toxic, and conferred resistance to oxidative stress.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Shinde
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Shaonan
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Douglas
authors.initials: D
authors.lastname: Holt
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Julie
authors.initials: J
authors.lastname: Goff
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Donna
authors.initials: D
authors.lastname: Shields
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Darcy
authors.initials: D
authors.lastname: Franicola
authors.affiliation: Department of Chemistry and Ctr. for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A. greenbergerjs@upmc.edu.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002460:Cell Line; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D009589:Nitrogen Oxides / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: C544775:JP4-039; D009589:Nitrogen Oxides
keywords: GS-Nitroxide; JP4-039; long-term bone marrow culture; radioresistance