Improved gene expression biodosimetry for dose estimation using an expanded panel of radiation-responsive genes

Area of Science:

• Radiation biology
• Molecular diagnostics
• Genomics

Background:

• Gene expression analysis offers a minimally invasive method for biological dosimetry.
• Current methods require improvement for point-of-care applications.

Purpose of the Study:

• To establish and validate an enhanced gene expression biodosimetry system.
• To utilize an expanded panel of radiation-responsive genes in human peripheral blood.

Main Methods:

• Irradiated human cells and peripheral blood with ⁶⁰Co γ-rays at various doses (0-8 Gy).
• Characterized expression of candidate genes (ZMAT3, SESN1, AEN, TRIAP1) and other radiation-responsive genes.
• Investigated dose rates (0.2-2 Gy/min) and developed multi-gene models using stepwise regression.

Main Results:

• Candidate genes showed dose-dependent expression 6-48h post-irradiation, unaffected by dose rate.
• Strong linear relationships (R² > 0.90) observed between log2 dose and ΔCt values.
• Optimized multi-gene models achieved high predictive accuracy (R² = 0.81-0.89) and validated in independent cohorts.

Conclusions:

• Expanded the repertoire of reliable radiation biomarkers.
• Developed optimized multi-gene models for precise radiation dose estimation.
• Advanced the standardization and clinical utility of gene expression biodosimetry.