title: Effects of the bifunctional sulfoxide MMS350, a radiation mitigator, on hematopoiesis in long-term bone marrow cultures and on radioresistance of marrow stromal cell lines.
abstract: The ionizing irradiation mitigator MMS350 prolongs survival of mice treated with total-body irradiation and prevents radiation-induced pulmonary fibrosis when added to drinking water at day 100 after thoracic irradiation. The effects of MMS350 on hematopoiesis in long-term bone marrow culture and on the radiobiology of derived bone marrow stromal cell lines were tested. Long-term bone marrow cultures were established from C57BL/6NTac mice and maintained in a high-humidity incubator, with 7% CO2 and the addition of 100 μM MMS350 at the weekly media change. Over 10 weeks in culture, MMS350 had no significant effect on maintenance of hematopoietic stem cell production, or on nonadherent cells or colony-forming units of hematopoietic progenitor cells. Stromal cell lines derived from non MMS350-treated long-term cultures or control stromal cells treated with MMS350 were radioresistant in the clonogenic survival curve assay. MMS350 is a non-toxic, highly water-soluble radiation mitigator that exhibits radioprotective effects on bone marrow stromal cells.
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors: Ashwin
authors: A
authors: Shinde
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors: Michael W
authors: MW
authors: Epperly
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors: Shaonan
authors: S
authors: Cao
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors: Darcy
authors: D
authors: Franicola
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors: Donna
authors: D
authors: Shields
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors: Hong
authors: H
authors: Wang
authors: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A. Center For Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors: Peter
authors: P
authors: Wipf
authors: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A. Center For Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors: Melissa M
authors: MM
authors: Sprachman
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A. greenbergerjs@upmc.edu.
authors: Joel S
authors: JS
authors: Greenberger
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000528:radiation effects*; D002460:Cell Line; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D004988:Ethers, Cyclic / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D051379:Mice; D011836:Radiation Tolerance / Q000187:drug effects* / Q000235:genetics; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017154:Stromal Cells; D013454:Sulfoxides / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D004988:Ethers, Cyclic; C586473:MMS350; D011837:Radiation-Protective Agents; D013454:Sulfoxides
keywords: Bifunctional sulfoxide; MMS350; hematopoiesis