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

Neetha Nanoth Vellichirammal; Sahil Sethi; Sanjit Pandey; Jatinder Singh; Stephen Y Wise; Alana D Carpenter; Oluseyi O Fatanmi; Chittibabu Guda; Vijay K Singh

doi:10.1016/j.omtn.2022.08.006

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

Mol Ther Nucleic Acids. 2022 Aug 4:29:584-598. doi: 10.1016/j.omtn.2022.08.006. eCollection 2022 Sep 13.

Authors

Neetha Nanoth Vellichirammal¹, Sahil Sethi¹, Sanjit Pandey¹, Jatinder Singh^{2

3}, Stephen Y Wise^{2

3}, Alana D Carpenter^{2

3}, Oluseyi O Fatanmi^{2

3}, Chittibabu Guda¹, Vijay K Singh^{2

3}

Affiliations

¹ Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
² 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.
³ Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

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.

Keywords: MT: bioinformatics; lung; nonhuman primates; partial-body irradiation; radiation countermeasure; radiation injury; total-body irradiation; transcriptomics; γ-tocotrienol.