Investigations into the role of inflammation in normal tissue response to irradiation.
Investigations into the role of inflammation in normal tissue response to irradiation.
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DOI：
10.1016/j.radonc.2011.06.017
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Jelveh S
中科院分区：
文献类型：
--
作者：
Hill RP;Zaidi A;Mahmood J;Jelveh S
辐射引起的炎症和活性氧 (ROS) 的产生在正常组织反应中发挥着关键作用。在这项研究中，我们检查了这些对肺和皮肤影响的某些方面。照射后给予超氧化物歧化酶 (SOD) 过氧化氢酶模拟物 EUK-207 和金雀异黄酮（一种具有抗炎特性的异黄酮），并测定来自受照射肺和皮肤的细胞中微核 (MN) 的形成。对肿瘤坏死因子 (TNF)-α 或其受体 TNFR1/2 敲除或用内毒素（脂多糖 - LPS）处理的 C57Bl6 小鼠进行照射后，使用体积描记器测量呼吸频率的变化。辐射后给予 EUK-207 和金雀异黄酮均导致辐射后 14 周内肺细胞中观察到的 MN 水平大幅下降，但停止治疗导致辐射后 28 周内 MN 水平反弹。相比之下，EUK-207 治疗对于减少辐射后皮肤细胞中观察到的 MN 基本上无效。相对于野生型和 TNFR1/2 敲除，TNF-α 敲除导致呼吸频率增加减少（照射后 12 周达到峰值）。照射后 1 小时用 LPS 治疗也减少了呼吸频率的增加。 EUK-207 或金雀异黄素治疗停止后，肺细胞中 MN 的产生表明，持续的 ROS 产生会导致肺细胞长期 DNA 损伤。在皮肤中没有看到这种效应表明这种机制在这种组织中不太明显。 TNF-α 敲除的动物中放射性肺炎水平降低（通过呼吸频率变化监测）表明这种细胞因子在辐射后诱导肺部炎症中发挥着重要作用。照射后给予 LPS 后观察到的类似效果表明，这种治疗可能会改变肺部照射后的长期周期性炎症反应。
Radiation-induced inflammation and production of reactive oxygen species (ROS) play a critical role in normal tissue response. In this study we have examined some aspects of these effects in lung and skin. The superoxide dismutase (SOD) catalase mimetic, EUK-207, and genistein, an isoflavone with anti-inflammatory properties, were given post irradiation and micronuclei (MN) formation was determined in cells derived from irradiated lung and skin. Changes in breathing rate were measured using a plethysmograph following irradiation of C57Bl6 mice knocked out for tumour necrosis factor (TNF)-alpha or its receptors, TNFR1/2, or treated with endotoxin (lipopolysaccharide - LPS). Both EUK-207 and genistein given after irradiation caused a large reduction in MN levels observed in lung cells during 14 weeks post-irradiation but ceasing treatment resulted in a rebound in MN levels at 28 weeks post-irradiation. In contrast, treatment with EUK-207 was largely ineffective in reducing MN observed in skin cells post-irradiation. Knock-out of TNF-alpha resulted in a reduced increase in breathing rate (peak at 12 weeks post-irradiation) relative to wild-type and TNFR1/2 knockout. Treatment with LPS 1 hour post-irradiation also reduced the increase in breathing rate. The generation of MN in lung cells after treatment with EUK-207 or genistein was stopped suggests that continuing ROS production contributes to DNA damage in lung cells over prolonged periods. That this effect was not seen in skin suggests this mechanism is less prominent in this tissue. The reduced level of radiation pneumonitis (as monitored by breathing rate changes) in animals knocked out for TNF-alpha suggests that this cytokine plays a significant role in inducing inflammation in lung following irradiation. The similar effect observed following LPS given post-irradiation suggests the possibility that such treatment modifies the long-term cyclic inflammatory response following irradiation in lung.
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