Tocopherol succinate: modulation of antioxidant enzymes and oncogene expression, and hematopoietic recovery.
OBJECTIVE
A class of naturally occurring isoforms of tocopherol (tocols) was shown to have varying degrees of protection when administered before radiation exposure. We recently demonstrated that α-tocopherol succinate (TS) is a potential radiation prophylactic agent. Our objective in this study was to further investigate the mechanism of action of TS in mice exposed to (60)Co γ-radiation.


METHODS
We evaluated the effects of TS on expression of antioxidant enzymes and oncogenes by quantitative RT-PCR in bone marrow cells of (60)Co γ-irradiated mice. Further, we tested the ability of TS to rescue and repopulate hematopoietic stem cells by analyzing bone marrow cellularity and spleen colony forming unit in spleen of TS-injected and irradiated mice.


RESULTS
Our results demonstrate that TS modulated the expression of antioxidant enzymes and inhibited expression of oncogenes in irradiated mice at different time points. TS also increased colony forming unit-spleen numbers and bone marrow cellularity in irradiated mice.


CONCLUSIONS
Results provide additional support for the observed radioprotective efficacy of TS and insight into mechanisms.
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA. singh@afrri.usuhs.mil
Vijay K
VK
Singh
Vaishali I
VI
Parekh
Darren S
DS
Brown
Tzu-Cheg
TC
Kao
Steven R
SR
Mog
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D003037:Cobalt Radioisotopes / Q000494:pharmacology; D003114:Colony-Forming Units Assay / Q000379:methods; D017931:DNA Primers / Q000235:genetics; D016758:Genes, jun / Q000187:drug effects / Q000528:radiation effects; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013249:Sternum / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; D003037:Cobalt Radioisotopes; D017931:DNA Primers; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D011837:Radiation-Protective Agents; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D024502:alpha-Tocopherol