title: Progenitor Cell Mobilization by Gamma-tocotrienol: A Promising Radiation Countermeasure.
abstract: This article reviews studies of progenitor mobilization with gamma-tocotrienol (GT3), a tocol under advanced development as a radiation countermeasure for acute radiation syndrome (ARS). GT3 protects mice against high doses of ionizing radiation and induces high levels of granulocyte colony-stimulating factor (G-CSF). GT3-induced G-CSF in conjunction with AMD3100 (a chemokine receptor antagonist clinically used to improve the yield of mobilized progenitors) mobilizes progenitors; these mobilized progenitors mitigate injury when infused to mice exposed to acute, high-dose ionizing radiation. The administration of a G-CSF antibody to GT3-injected donor mice abrogated the radiomitigative efficacy of blood or peripheral blood mononuclear cells (PBMC) in irradiated recipient mice. The efficacy of GT3-injected donor mice blood or PBMC was comparable to a recently published article involving blood or mononuclear cells obtained from mice injected with G-CSF. The injected progenitors were found to localize in various tissues of irradiated hosts. The authors demonstrate the efficacy of a bridging therapy in a preclinical animal model that allows the lymphohematopoietic system of severely immunocompromised mice to recover. This suggests that GT3 is a highly effective agent for radioprotection and mobilizing progenitors with significant therapeutic potential. Therefore, GT3 may be considered for further translational development and ultimately for use in humans.
authors.affiliation: *F. Edward Hébert School of Medicine, "America's Medical School;" †Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
authors.forename: Oluseyi O
authors.initials: OO
authors.lastname: Fatanmi
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Newman
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Wise
authors.forename: Patricia L P
authors.initials: PL
authors.lastname: Romaine
authors.forename: Allison N
authors.initials: AN
authors.lastname: Berg
mesh_terms: D054508:Acute Radiation Syndrome / Q000473:pathology* / Q000628:therapy*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D016896:Treatment Outcome; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D002839:Chromans; D011837:Radiation-Protective Agents; D014810:Vitamin E; C013649:plastochromanol 8