Multiwell-based G0-PCC assay for radiation biodosimetry

Area of Science:

• Radiation biology
• Cytogenetics
• Medical countermeasures

Background:

• Rapid detection of ionizing radiation exposure is critical for effective medical intervention during radiological events.
• Existing high-throughput cytogenetic biodosimetry assays require approximately 3 days for results, delaying critical treatment decisions.
• Accurate dose estimation is vital for patient care and epidemiological studies following radiation exposure.

Purpose of the Study:

• To develop a rapid, high-throughput cytogenetic assay for same-day detection and quantification of radiation exposure.
• To improve the speed of biodosimetry for immediate medical triage and long-term patient management.
• To establish a method for dose categorization and reconstruction in large-scale radiation emergencies.

Main Methods:

• Development of a multiwell-based variant of the chemical-induced G0-phase Premature Chromosome Condensation Assay.
• Optimization of phosphatase inhibitor concentration to enhance chromosome condensation and yield.
• Quantification of radiation-induced chromosome fragmentation using a custom Deep Learning algorithm.

Main Results:

• The modified Premature Chromosome Condensation Assay yields same-day results.
• Lower phosphatase inhibitor concentrations increased the yield of highly condensed chromosomes with dose-dependent fragmentation.
• The Deep Learning algorithm achieved 84% and 80% accuracy for categorizing doses into three and four iso-treatment bins, respectively.
• The algorithm demonstrated a correlation coefficient of 0.879 for determining actual radiation doses received.

Conclusions:

• This novel assay provides rapid, same-day cytogenetic biodosimetry for ionizing radiation exposure.
• The method is automatable and suitable for high-throughput analysis in radiation emergencies.
• It offers a significant improvement over existing methods for timely dose categorization and reconstruction.