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Impact of GADD45A on Radiation Biodosimetry Using Mouse Peripheral Blood
Constantinos G Broustas1, Sanjay Mukherjee1, Igor Shuryak1
1Center for Radiological Research, Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York 10032.
Radiation Research
|July 8, 2023
Summary
Radiation biodosimetry accurately assesses radiation exposure, even with pre-existing inflammation from GADD45A deficiency. Gene expression analysis reliably distinguishes irradiated from control mice, confirming its utility post-radiological incidents.
Area of Science:
- Radiation biology
- Genomics
- Immunology
Background:
- High-dose radiation exposure causes severe organ damage and mortality.
- Gene expression analysis of blood is crucial for radiation biodosimetry.
- Pre-existing inflammation can interfere with biodosimetry accuracy.
Purpose of the Study:
- To investigate the impact of GADD45A deficiency-induced inflammation on radiation biodosimetry.
- To determine if gene expression biodosimetry remains accurate in the presence of chronic inflammation.
Main Methods:
- Exposed wild-type and GADD45A knockout mice to 7 Gy X-rays.
- Isolated RNA from whole blood 24 hours post-irradiation.
- Performed whole genome microarray and gene ontology analyses.
- Utilized gene signatures for dose reconstruction.
Main Results:
- Radiation biodosimetry accurately reconstructed 0 Gy or 7 Gy doses in GADD45A knockout mice (RMSE ± 1.05 Gy).
- Irradiation significantly overrepresented cell death and morbidity pathways in both genotypes, more so in GADD45A-null mice.
- GADD45A deficiency exacerbated radiation's deleterious effects on blood cells, including T lymphocytes and myeloid cells, and increased risk of hematological malignancies.
Conclusions:
- Gene expression biodosimetry is feasible and accurate, even with pre-existing inflammation caused by GADD45A ablation.
- GADD45A deficiency amplifies radiation-induced damage and alters immune cell profiles.
- A reliable gene panel can distinguish irradiated from control individuals regardless of inflammation status.
