Nitric oxide radicals choreograph a radioadaptive response
Nitric oxide radicals choreograph a radioadaptive response
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DOI：
10.1158/0008-5472.can-07-1913
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发表时间：
2007-09-15
期刊：
影响因子：
11.2
通讯作者：
Ohnishi, Takeo
中科院分区：
文献类型：
--
作者：
Matsumoto, Hideki;Takahashi, Akihisa;Ohnishi, Takeo
细胞在低剂量或低剂量率条件照射后（即获得对高剂量辐射的抵抗力）所见的辐射照射的生物效应降低被称为“辐射适应反应”，自1980年代以来已报道了许多关于这一现象的研究。辐射适应反应已被观察到使用不同的终点，如染色体畸变、突变和克隆生存。然而，辐射适应性反应的机制尚不完全清楚。在这里，我们表明辐射诱导的一氧化氮（NO）自由基有助于诱导辐射抗性，这是由随后的高剂量暴露后的细胞存活决定的。当细胞以低剂量率暴露于伽马射线或低剂量暴露于x射线后再急性高剂量x射线照射时，培养基中亚硝酸盐浓度增加，产生可诱导的NO合成酶积累。此外，在诱导型NO合成酶抑制剂或NO自由基清除剂存在的情况下，没有观察到辐射抗性的诱导。此外，当培养物用NO自由基生成剂处理时，观察到辐射抗性。这些发现表明NO自由基是放射适应性反应的发起者。
The reduced biological effects of radiation exposure seen in cells after conditioning exposures to a low dose or at a low-dose rate (i.e., the acquisition of resistance against high-dose radiation) is called the "radioadaptive response" and many studies concerning this phenomenon have been reported since the 1980s. Radioadaptive responses have been observed using various end points, such as chromosomal aberrations, mutations, and clonogenic survival. However, the mechanisms of the radioadaptive response are not fully known. Here, we show that radiation-induced nitric oxide (NO) radicals contribute to the induction of radioresistance as determined by cell survival after a subsequent high-dose exposure. An accumulation of inducible NO synthase was produced, and the concentration of nitrite in the culture medium increased when cells were exposed to gamma-rays at a low-dose rate or to X-rays for a low dose followed by an acute high-dose X-irradiation. In addition, the induction of radioresistance was not observed in the presence of an inhibitor of inducible NO synthase or a scavenger of NO radicals. Moreover, radioresistance was observed when cultures were treated with a NO radical-generating agent. These findings suggest that NO radicals are an initiator of the radioadaptive response.