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用小鼠外周血液进行辐射生物对比的GADD45A的影响

Constantinos G Broustas¹, Sanjay Mukherjee¹, Igor Shuryak¹

¹Center for Radiological Research, Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York 10032.

Radiation research

|July 8, 2023

概括

辐射生物测量准确地评估了辐射暴露,即使是从GADD45A缺陷中预先存在的炎症. 基因表达分析可靠地区分了被照射和对照小鼠,证实了其在放射后事件中的实用性.

科学领域:

辐射生物学辐射生物学
基因组学就是基因组学.
免疫学免疫学免疫学

背景情况:

高剂量的辐射暴露会导致严重的器官损伤和死亡.
血液的基因表达分析对于辐射生物对称学至关重要.
预先存在的炎症可能会干扰生物对比度的准确性.

研究的目的:

为了研究GADD45A缺乏引起的炎症对辐射生物对称学的影响.
为了确定基因表达生物对称在出现慢性炎症时是否保持准确.

主要方法:

暴露于7 Gy X射线的野生型和GADD45A淘汰赛小鼠.
从全血中分离的RNA,在辐射后24小时.
进行了全基因组微阵列和基因本体学分析.
利用基因特征进行剂量重建.

主要成果:

辐射生物测量准确地重建了GADD45A淘汰赛小鼠中的0 Gy或7 Gy剂量 (RMSE ± 1.05 Gy).
在这两种基因型中,辐射显著过度代表了细胞死亡和发病途径,在GADD45A-null小鼠中更为如此.
缺乏GADD45A会加剧辐射对血液细胞的有害影响,包括T淋巴细胞和骨髓细胞,并增加了血液恶性瘤的风险.

结论:

基因表达生物对称是可行的和准确的,即使在由GADD45A剥离引起的先前存在的炎症.
缺乏GADD45A会放大辐射引起的损伤,并改变免疫细胞的形状.
一个可靠的基因组可以区分照射和控制个体,无论炎症状况如何.

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