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Gene Expression Profiles from Heart, Lung and Liver Samples of Total-Body-Irradiated Minipigs: Implications for Predicting Radiation-Induced Tissue Toxicity.
Radiation Research ( IF 3.4 ) Pub Date : 2020-09-16 , DOI: 10.1667/rade-20-00123.1
Sunita Chopra 1 , Maria Moroni 2 , Shannon Martello 1 , Michelle Bylicky 1 , Jared May 1 , Bernadette Hritzo 2 , Laurel MacMillan 3 , C Norman Coleman 1, 4 , Molykutty J Aryankalayil 1
Affiliation  

In the event of a major accidental or intentional radiation exposure incident, the affected population could suffer from total- or partial-body exposures to ionizing radiation with acute exposure to organs that would produce life-threatening injury. Therefore, it is necessary to identify markers capable of predicting organ-specific damage so that appropriate directed or encompassing therapies can be applied. In the current work, gene expression changes in response to total-body irradiation (TBI) were identified in heart, lungs and liver tissue of Göttingen minipigs. Animals received 1.7, 1.9, 2.1 or 2.3 Gy TBI and were followed for 45 days. Organ samples were collected at the end of day 45 or sooner if the animal displayed morbidity necessitating euthanasia. Our findings indicate that different organs respond to TBI in a very specific and distinct manner. We also found that the liver was the most affected organ in terms of gene expression changes, and that lipid metabolic pathways were the most deregulated in the liver samples of non-survivors (survival time <45 days). We identified organ-specific gene expression signatures that accurately differentiated non-survivors from survivors and control animals, irrespective of dose and time postirradiation. At what point did these radiation-induced injury markers manifest and how this information could be used for applying intervention therapies are under investigation.



中文翻译:

全身照射小型猪心脏、肺和肝脏样本的基因表达谱:预测辐射诱导的组织毒性的意义。

如果发生重大的意外或故意辐射照射事件,受影响的人群可能会遭受全身或部分身体的电离辐射照射,器官急性照射会产生危及生命的伤害。因此,有必要识别能够预测器官特异性损伤的标志物,以便可以应用适当的定向或综合疗法。在目前的工作中,在哥廷根小型猪的心脏、肺和肝脏组织中发现了响应于全身照射 (TBI) 的基因表达变化。动物接受 1.7、1.9、2.1 或 2.3 Gy TBI 并随访 45 天。如果动物表现出需要安乐死的发病率,则在第 45 天或更早时收集器官样本。我们的研究结果表明,不同的器官以非常具体和独特的方式对 TBI 作出反应。我们还发现,就基因表达变化而言,肝脏是受影响最严重的器官,并且脂质代谢途径在非幸存者的肝脏样本中最为失调(存活时间 <45 天)。我们确定了器官特异性基因表达特征,可准确区分非幸存者与幸存者和对照动物,而与照射后的剂量和时间无关。这些辐射诱发的损伤标志物在什么时候表现出来,以及如何将这些信息用于应用干预疗法正在调查中。并且脂质代谢途径在非幸存者的肝脏样本中最为失调(存活时间<45天)。我们确定了器官特异性基因表达特征,可准确区分非幸存者与幸存者和对照动物,而与照射后的剂量和时间无关。这些辐射诱发的损伤标志物在什么时候表现出来,以及如何将这些信息用于应用干预疗法正在调查中。并且脂质代谢途径在非幸存者的肝脏样本中最为失调(存活时间<45天)。我们确定了器官特异性基因表达特征,可准确区分非幸存者与幸存者和对照动物,而与照射后的剂量和时间无关。这些辐射诱发的损伤标志物在什么时候表现出来,以及如何将这些信息用于应用干预疗法正在调查中。

更新日期:2020-10-12
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