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