Radioprotective efficacy of delta-tocotrienol, a vitamin E isoform, is mediated through granulocyte colony-stimulating factor.
OBJECTIVE
The objectives of this study were to determine the cytokine induction by delta tocotrienol (DT3, a promising radiation countermeasure) and to investigate the role of granulocyte colony-stimulating factor (G-CSF) in its radioprotective efficacy against ionizing radiation in mice.


METHODS
Multiplex Luminex was used to analyze cytokines induced by DT3 and other tocols (gamma-tocotrienol and tocopherol succinate) in CD2F1 mice. Mice were injected with an optimal dose of DT3 and a G-CSF antibody, and their 30-day survival against cobalt-60 gamma-irradiation was monitored. The neutralization of G-CSF by the administration of a G-CSF-specific antibody in DT3-injected mice was investigated by multiplex Luminex.


RESULTS
Our data demonstrate that DT3 induced high levels of various cytokines comparable to other tocols being developed as radiation countermeasures. DT3 significantly protected mice against ionizing radiation, and the administration of a G-CSF neutralizing antibody to DT3-treated animals resulted in the complete abrogation of DT3's radioprotective efficacy and neutralization of G-CSF in peripheral blood.


CONCLUSIONS
Our study findings suggest that G-CSF induced by DT3 mediates its radioprotective efficacy against ionizing radiation in mice.
Armed Forces Radiobiology Research Institute, Bethesda, MD, USA; Department of Radiation Biology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address: vijay.singh@usuhs.edu.
Vijay K
VK
Singh
Armed Forces Radiobiology Research Institute, Bethesda, MD, USA.
Stephen Y
SY
Wise
Armed Forces Radiobiology Research Institute, Bethesda, MD, USA.
Jessica R
JR
Scott
Armed Forces Radiobiology Research Institute, Bethesda, MD, USA.
Patricia L P
PL
Romaine
Armed Forces Radiobiology Research Institute, Bethesda, MD, USA.
Victoria L
VL
Newman
Armed Forces Radiobiology Research Institute, Bethesda, MD, USA.
Oluseyi O
OO
Fatanmi
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D055104:Infusions, Subcutaneous; D008297:Male; D051379:Mice; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D016207:Cytokines; D011837:Radiation-Protective Agents; D014810:Vitamin E; D016179:Granulocyte Colony-Stimulating Factor; C082097:tocotrienol, delta
Delta-tocotrienol; Gamma-radiation; Granulocyte colony-stimulating factor; Mice; Radiation; Tocols