期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 29, 期 -, 页码 584-598出版社
CELL PRESS
DOI: 10.1016/j.omtn.2022.08.006
关键词
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资金
- Bioinformatics and Systems Biology Core (BSBC) facility at University of Nebraska Medical Center
- Nebraska Research Initiative (NRI)
- NIH [2P20GM103427, 5P30CA036727, 2U54GM115458]
- NRI
The study investigated the impact of a supralethal dose of radiation on alterations in the lung transcriptome using a nonhuman primate model. Significant radiation-induced changes in the lung transcriptome were observed for both total-body irradiation (TBI) and partial-body irradiation (PBI), with common signaling pathways being upregulated in both exposures.
The focus of radiation biodosimetry has changed recently, and a paradigm shift for using molecular technologies of omic platforms in addition to cytogenetic techniques has been observed. In our study, we have used a nonhuman primate model to investigate the impact of a supralethal dose of 12 Gy radiation on alterations in the lung transcriptome. We used 6 healthy and 32 irradiated animal samples to delineate radiation-induced changes. We also used a medical countermeasure, gamma-tocotrienol (GT3), to observe any changes. We demonstrate significant radiation-induced changes in the lung transcriptome for total-body irradiation (TBI) and partial-body irradiation (PBI). However, no major influence of GT3 on radiation was noted in either comparison. Several common signaling pathways, including PI3K/AKT, GADD45, and p53, were upregulated in both exposures. TBI activated DNA-damage-related pathways in the lungs, whereas PTEN signaling was activated after PBI. Our study highlights the various transcriptional profiles associated with gamma- and X-ray exposures, and the associated pathways include LXR/RXR activation in TBI, whereas pulmonary wound-healing and pulmonary fibrosis signaling was repressed in PBI. Our study provides important insights into the molecular pathways associated with irradiation that can be further investigated for biomarker discovery.
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