Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation

BMC Genomics

Research

Sahil Sethi¹  Nagavardhini Avuthu¹  Neetha Nanoth Vellichirammal¹  Chittibabu Guda¹  Oluseyi O. Fatanmi²  Vijay K. Singh²  Stephen Y. Wise²  Alana D. Carpenter² 

[1] Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, 68198, Omaha, NE, USA;Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA;Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA;

关键词: Gamma tocotrienol;    Jejunum, Nonhuman primates;    Radiation injury;    Radiation countermeasure;    Transcriptomics, Total-body irradiation, Partial-body irradiation;   

DOI  :  10.1186/s12864-023-09385-3

 received in 2023-01-19, accepted in 2023-05-17,  发布年份 2023

来源: Springer

【 摘 要 】

The risk of exposure of the general public or military personnel to high levels of ionizing radiation from nuclear weapons or radiological accidents is a dire national security matter. The development of advanced molecular biodosimetry methods, those that measure biological response, such as transcriptomics, to screen large populations of radiation-exposed victims is key to improving survival outcomes during radiological mass casualty scenarios. In this study, nonhuman primates were exposed to either 12.0 Gy cobalt-60 gamma (total-body irradiation, TBI) or X-ray (partial-body irradiation, PBI) 24 h after administration of a potential radiation medical countermeasure, gamma-tocotrienol (GT3). Changes in the jejunal transcriptomic profiles in GT3-treated and irradiated animals were compared to healthy controls to assess the extent of radiation damage. No major effect of GT3 on radiation-induced transcriptome at this radiation dose was identified. About 80% of the pathways with a known activation or repression state were commonly observed between both exposures. Several common pathways activated due to irradiation include FAK signaling, CREB signaling in the neurons, phagosome formation, and G-protein coupled signaling pathway. Sex-specific differences associated with excessive mortality among irradiated females were identified in this study, including Estrogen receptor signaling. Differential pathway activation was also identified across PBI and TBI, pointing towards altered molecular response for different degrees of bone marrow sparing and radiation doses. This study provides insight into radiation-induced changes in jejunal transcriptional profiles, supporting the investigation for the identification of biomarkers for radiation injury and countermeasure efficacy.

【 授权许可】

CC BY   
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

【 图 表 】

41116_2023_36_Article_IEq396.gif

41116_2023_36_Article_IEq391.gif

41116_2023_36_Article_IEq388.gif

41116_2023_36_Article_IEq384.gif

41116_2023_36_Article_IEq380.gif

41116_2023_36_Article_IEq378.gif