Li Yaoxiang, Singh Jatinder, Varghese Rency, Zhang Yubo, Fatanmi Oluseyi O, Cheema Amrita K, Singh Vijay K
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine "America's Medical School", Uniformed Serices University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, USA.
Sci Rep. 2021 Mar 18;11(1):6295. doi: 10.1038/s41598-021-85669-6.
The field of biodosimetry has seen a paradigm shift towards an increased use of molecular phenotyping technologies including omics and miRNA, in addition to conventional cytogenetic techniques. Here, we have used a nonhuman primate (NHP) model to study the impact of gamma-irradiation on alterations in blood-based gene expression. With a goal to delineate radiation induced changes in gene expression, we followed eight NHPs for 60 days after exposure to 6.5 Gy gamma-radiation for survival outcomes. Analysis of differential gene expression in response to radiation exposure yielded 26,944 dysregulated genes that were not significantly impacted by sex. Further analysis showed an increased association of several pathways including IL-3 signaling, ephrin receptor signaling, ErbB signaling, nitric oxide signaling in the cardiovascular system, Wnt/β-catenin signaling, and inflammasome pathway, which were associated with positive survival outcomes in NHPs after acute exposure to radiation. This study provides novel insights into major pathways and networks involved in radiation-induced injuries that may identify biomarkers for radiation injury.
生物剂量测定领域已经发生了范式转变,除了传统的细胞遗传学技术外,分子表型技术(包括组学和微小RNA)的使用也日益增加。在此,我们使用了非人类灵长类动物(NHP)模型来研究γ射线照射对血液中基因表达变化的影响。为了描绘辐射诱导的基因表达变化,我们在8只NHP暴露于6.5 Gy γ射线后跟踪观察60天,以了解生存结果。对辐射暴露后差异基因表达的分析产生了26944个失调基因,这些基因不受性别的显著影响。进一步分析表明,包括IL-3信号传导、 Ephrin受体信号传导、 ErbB信号传导、心血管系统中的一氧化氮信号传导、 Wnt/β-连环蛋白信号传导和炎性小体途径在内的几种途径之间的关联增加,这些途径与急性辐射暴露后NHP的阳性生存结果相关。这项研究为辐射诱导损伤所涉及的主要途径和网络提供了新的见解,可能有助于识别辐射损伤的生物标志物。