Elevated DNA damage in a mouse model of oxidative stress: impacts of ionizing radiation and a protective dietary supplement
Elevated DNA damage in a mouse model of oxidative stress: impacts of ionizing radiation and a protective dietary supplement
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DOI：
10.1093/mutage/gen036
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发表时间：
2008-11-01
期刊：
影响因子：
2.7
通讯作者：
Boreham, D. R.
中科院分区：
文献类型：
--
作者：
Lemon, J. A.;Rollo, C. D.;Boreham, D. R.
转基因生长激素（Tg）小鼠表达升高的自由基过程和加速老化的早衰综合征。我们检查了骨髓细胞的转基因小鼠和他们的正常（Nr）的兄弟姐妹的三个标志物的DNA损伤和评估的影响，自由基应激使用电离辐射。我们还评估了膳食补充剂提供的辐射保护，我们以前证明了该膳食补充剂可以延长Nr和Tg小鼠的寿命并减少其认知老化。光谱核型分析显示Nr或Tg中很少有自发染色体畸变。然而，与Nr小鼠相比，Tg小鼠具有显著更高的γ H2 AX和8-羟基-脱氧鸟苷（8-OHdG）的组成性水平。当暴露于2-戈伊全身剂量的电离辐射时，Nr和Tg小鼠的DNA损伤均显著增加。与Nr小鼠相比，辐照的Tg小鼠具有显著更高水平的γ H2 AX病灶和两倍的染色体畸变水平。在未照射的小鼠中，膳食补充剂显著降低了Nr和Tg小鼠中的组成型γ H2 AX和8-OHdG（使Tg中的γ H2 AX和8-OHdG均正常化），γ H2 AX和8-OHdG在组成型水平上几乎没有差异。诱导的染色体畸变也减少了，在Nr小鼠中几乎不存在。值得注意的是，与未补充的Nr或Tg小鼠相比，补充的小鼠表达的辐射诱导的染色体畸变水平低6倍。根据我们的数据，膳食补充剂似乎可以在自由基造成损害之前阻止它们。这项研究验证了Tg小鼠作为氧化应激和辐射超敏反应的示例性模型，并记录了由公众可用成分组成的膳食补充剂的前所未有的辐射防护作用。
Transgenic growth hormone (Tg) mice express elevated free radical processes and a progeroid syndrome of accelerated ageing. We examined bone marrow cells of Tg mice and their normal (Nr) siblings for three markers of DNA damage and assessed the impact of free radical stress using ionizing radiation. We also evaluated the radiation protection afforded by a dietary supplement that we previously demonstrated to extend longevity and reduce cognitive ageing of Nr and Tg mice. Spectral karyotyping revealed few spontaneous chromosomal aberrations in Nr or Tg. Tg mice, however, had significantly greater constitutive levels of both gamma H2AX and 8-hydroxy-deoxyguanosine (8-OHdG) compared to Nr. When exposed to a 2-Gy whole-body dose of ionizing radiation, both Nr and Tg mice showed significant increases in DNA damage. Compared to Nr mice, irradiated Tg mice had dramatically higher levels of gamma H2AX foci and double the levels of chromosomal aberrations. In unirradiated mice, the dietary supplement significantly reduced constitutive gamma H2AX and 8-OHdG in both Nr and Tg mice (normalizing both gamma H2AX and 8-OHdG in Tg), with little difference in gamma H2AX and 8-OHdG over constitutive levels. Induced chromosomal aberrations were also reduced, and in Nr mice, virtually absent. Remarkably, supplemented mice expressed 6-fold lower levels of radiation-induced chromosomal aberrations compared to unsupplemented Nr or Tg mice. Based on our data, the dietary supplement appeared to scavenge free radicals before they could cause damage. This study validates Tg mice as an exemplary model of oxidative stress and radiation hypersensitivity and documents unprecedented radioprotection by a dietary supplement comprised of ingredients available to the general public.