Developing Human Radiation Biodosimetry Models: Testing Cross-Species Conversion Approaches Using an Ex Vivo Model...

Area of Science:

• Radiation biology
• Genomics
• Biodosimetry

Background:

• Accurate radiation dose assessment is critical for managing large-scale radiation exposures.
• Current biodosimetry methods are time-consuming and require specialized expertise.
• Gene expression profiling offers a scalable alternative, but human sample scarcity necessitates animal models.

Purpose of the Study:

• To investigate the feasibility of using non-human primate (NHP) models for developing human radiation biodosimetry algorithms.
• To compare gene expression profiles in human and NHP blood samples after radiation exposure.
• To develop and validate a cross-species biodosimetry model.

Main Methods:

• Irradiation of ex vivo peripheral blood samples from humans and rhesus macaques with varying radiation doses (0-7 Gy).
• Comparison of gene expression profiles using Agilent human microarrays 24 hours post-irradiation.
• Development of biodosimetry models using interspecies-correlated genes and cross-species expression conversion techniques.

Main Results:

• Fifty-two dose-responsive genes showed correlated expression patterns between humans and NHPs, enriched in DNA damage and cell cycle pathways.
• NHP-based biodosimetry models achieved ~90% prediction accuracy for NHP samples within 1 Gy.
• A multi-gene cross-species conversion approach yielded up to 94% prediction accuracy for human samples using the NHP model.

Conclusions:

• Non-human primates are suitable models for building robust radiation biodosimetry algorithms.
• Interspecies-correlated genes and cross-species expression conversion are key to accurate human dose prediction.
• This approach significantly enhances the scalability and applicability of biodosimetry for radiation emergencies.