TOCOPHEROL SUCCINATE: MODULATION OF ANTIOXIDANT ENZYMES AND ONCOGENE EXPRESSION, AND HEMATOPOIETIC RECOVERY

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 a-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 Co-60 gamma-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 Co-60 gamma-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. (C) 2011 Elsevier Inc.