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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)584-598
Number of pages15
JournalMolecular Therapy - Nucleic Acids
Volume29
DOIs
StatePublished - Sep 13 2022

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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