Evaluation of Potential Ionizing Irradiation Protectors and Mitigators Using Clonogenic Survival of Human Umbilical Cord Blood Hematopoietic Progenitor Cells

Julie P. Goff; Donna S. Shields; Hong Wang; Erin M. Skoda; Melissa M. Sprachman; Peter Wipf; Venkata Krishna Garapati; Jeffrey Atkinson; Barry London; John S. Lazo; Valerian Kagan; Michael W. Epperly; Joel S. Greenberger

doi:10.1016/j.exphem.2013.08.001

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Evaluation of Potential Ionizing Irradiation Protectors and Mitigators Using Clonogenic Survival of Human Umbilical Cord Blood Hematopoietic Progenitor Cells

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Evaluation of Potential Ionizing Irradiation Protectors and Mitigators Using Clonogenic Survival of Human Umbilical Cord Blood Hematopoietic Progenitor Cells

Julie P. Goff, Donna S. Shields, Hong Wang, Erin M. Skoda, Melissa M. Sprachman, Peter Wipf, Venkata Krishna Garapati, Jeffrey Atkinson, Barry London, John S. Lazo, …

Experimental hematology, Vol.41(11), pp.957-966

08/07/2013

DOI: 10.1016/j.exphem.2013.08.001

PMCID: PMC3834150

PMID: 23933481

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Abstract

We evaluated the use of colony formation (CFU-GM, BFU-E, and CFU-GEMM) by human umbilical cord blood (CB) hematopoietic progenitor cells for testing novel small molecule ionizing irradiation protectors and mitigators. Each of 11 compounds was added before (protection) or after (mitigation) ionizing irradiation including: GS-nitroxides (JP4-039 and XJB-5-131), the bifunctional sulfoxide MMS-350, the phosphoinositol-3-kinase inhibitor (LY294002), TPP-imidazole fatty acid, (TPP-IOA), the nitric oxide synthase inhibitor (MCF-201-89), the p53/mdm2/mdm4 inhibitor (BEB55), methoxamine, isoproterenol, propanolol, and the ATP sensitive potassium channel blocker (glyburide). The drugs XJB-5-131, JP4-039, and MMS-350 were radiation protectors for CFU-GM. JP4-039 was also a radiation protector for CFU-GEMM. The drugs, XJB-5-131, JP4-039, and MMS-350 were radiation mitigators for BFU-E, MMS-350 and JP4-039 were mitigators for CFU-GM, and MMS350 was a mitigator for CFU-GEMM. In contrast, other drugs that were effective in murine assays: TTP-IOA, LY294002, MCF201-89, BEB55, propranolol, isoproterenol, methoxamine, and glyburide showed no significant protection or mitigation in human CB assays. These data support testing of new candidate clinical radiation protectors and mitigators using human CB clonogenic assays early in the drug discovery process, reducing the need for animal experiments.

cord blood

radiation mitigation

radiosensitivity

therapeutics

Details

Title: Subtitle: Evaluation of Potential Ionizing Irradiation Protectors and Mitigators Using Clonogenic Survival of Human Umbilical Cord Blood Hematopoietic Progenitor Cells
Creators: Julie P. Goff - University of Pittsburgh
Donna S. Shields - University of Pittsburgh
Hong Wang - University of Pittsburgh
Erin M. Skoda - University of Pittsburgh
Melissa M. Sprachman - University of Pittsburgh
Peter Wipf - University of Pittsburgh
Venkata Krishna Garapati - Brock University
Jeffrey Atkinson - Brock University
Barry London - University of Iowa
John S. Lazo - University of Virginia
Valerian Kagan - University of Pittsburgh
Michael W. Epperly - University of Pittsburgh
Joel S. Greenberger - University of Pittsburgh
Resource Type: Journal article
Publication Details: Experimental hematology, Vol.41(11), pp.957-966
DOI: 10.1016/j.exphem.2013.08.001
PMID: 23933481
PMCID: PMC3834150
NLM abbreviation: Exp Hematol
ISSN: 0301-472X
eISSN: 1873-2399
Grant note: U19 AI068021 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
Language: English
Date published: 08/07/2013
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984297503902771

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