Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA.
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.
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.
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.
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.
Results provide additional support for the observed radioprotective efficacy of TS and insight into mechanisms.
研究表明,生育酚(tocols)的一类天然存在的同工型在辐射暴露前给药时具有不同程度的保护作用。我们最近证明α-生育酚琥珀酸酯(TS)是一种有潜力的辐射预防剂。本研究的目的是进一步研究 TS 在接受(60)Coγ射线照射的小鼠中的作用机制。
我们通过定量 RT-PCR 评估了 TS 在(60)Coγ辐射照射的小鼠骨髓细胞中对抗氧化酶和癌基因表达的影响。此外,我们通过分析 TS 注射和照射小鼠的骨髓细胞计数和脾集落形成单位来测试 TS 拯救和再生成造血干细胞的能力。
我们的结果表明,TS 在不同时间点调节了抗氧化酶的表达,并抑制了辐照小鼠癌基因的表达。TS 还增加了辐照小鼠脾集落形成单位-脾的数量和骨髓细胞计数。
这些结果为观察到的 TS 的放射防护效果提供了额外的支持,并深入了解了相关机制。