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Lung transcriptome of nonhuman primates exposed to total- and partial-body irradiation

Authors :
Neetha Nanoth Vellichirammal
Sahil Sethi
Sanjit Pandey
Jatinder Singh
Stephen Y. Wise
Alana D. Carpenter
Oluseyi O. Fatanmi
Chittibabu Guda
Vijay K. Singh
Source :
Molecular therapy. Nucleic acids. 29
Publication Year :
2022

Abstract

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, γ-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 γ- 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.

Subjects

Subjects :
Drug Discovery
Molecular Medicine

Details

ISSN :
21622531
Volume :
29
Database :
OpenAIRE
Journal :
Molecular therapy. Nucleic acids
Accession number :
edsair.doi.dedup.....4b049cb9219f660e64c5eaf70d6db4fa