整合多omics和基准剂量建模,以支持不良结果途径
Ngoc Q Vuong1, Saadia Khilji1, Andrew Williams2
1Radiation Protection Bureau, Health Canada, Ottawa, ON, Canada.
International journal of radiation biology
|January 2, 2025
概括
这项研究使用了omics和基准剂量 (BMD) 建模来确定与急性髓性白血病发展关键事件相关的辐射剂量. 这些发现有助于评估低剂量辐射暴露的风险.
科学领域:
- 辐射毒理学 辐射毒理学
- 系统生物学 系统生物学
- 基因组学和蛋白质组学
背景情况:
- 奥米克技术和基准剂量 (BMD) 建模推进了导致特定生物变化的剂量的识别.
- 不良结果途径 (AOPs) 通过关键事件 (KEs) 将毒素与不良影响联系起来.
- 将omics数据与AOP集成,可以从数量上将分子事件与表型结果联系起来.
研究的目的:
- 在暴露于辐射的体外血液模型中应用基于OMICS的BMD分析.
- 为了确定导致急性髓性白血病 (AOP 432) 的关键事件 (KEs) 的起点 (POD) 值.
主要方法:
- 白细胞被培养并暴露在X辐射中.
- 在暴露后24小时分析了转录和蛋白质变化.
- BMD建模确定了与AOP 432 KEs相关的扰乱基因,蛋白质和途径.
主要成果:
- BMD建模确定了1294个基因和167个蛋白质,其 BMD 的中位数下限值分别为1.35和0.32 Gy.
- 途径分析揭示了包括DNA损伤/修复,氧化应激,细胞循环调节,免疫反应和癌症发展在内的过程,与AOP 432 KEs.
- 与KES相关的途径的BMDL值通常低于0.5 Gy,一些基因显示BMDL<0.05 Gy.
结论:
- 这项研究提供了关于辐射诱导效应预测机制的见解.
- 通过确定相关的活性剂量,这些发现为低剂量辐射 (<0.1 Gy) 的风险分析提供了信息.
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