Tocopherol succinate: modulation of antioxidant enzymes and oncogene expression, and hematopoietic recovery

Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):571-8. doi: 10.1016/j.ijrobp.2010.08.019. Epub 2010 Oct 13.

Abstract

Purpose: 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 and materials: 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.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / radiation effects
  • Cobalt Radioisotopes / pharmacology
  • Colony-Forming Units Assay / methods
  • DNA Primers / genetics
  • Genes, jun / drug effects
  • Genes, jun / radiation effects
  • Glutathione Peroxidase / drug effects
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / drug effects
  • Glutathione Reductase / metabolism
  • Glutathione Transferase / drug effects
  • Glutathione Transferase / metabolism
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / physiology
  • Hematopoietic Stem Cells / radiation effects
  • Male
  • Mice
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Radiation-Protective Agents / pharmacology*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / radiation effects
  • Sternum / cytology
  • Sternum / drug effects
  • Sternum / radiation effects
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / metabolism
  • alpha-Tocopherol / pharmacology*

Substances

  • Antioxidants
  • Cobalt Radioisotopes
  • DNA Primers
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-myc
  • Radiation-Protective Agents
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Glutathione Transferase
  • alpha-Tocopherol