Radiation Biological Toximetry Using Circulating Cell-Free DNA (cfDNA) for Rapid Radiation/Nuclear Triage.

Area of Science:

• Radiation biology
• Molecular diagnostics
• Biomarker discovery

Background:

• Optimal biodosimetry requires rapid risk stratification applicable across diverse patient factors.
• Current methods face limitations in speed and applicability.
• Cell-free DNA (cfDNA) concentration is a potential biomarker for radiation exposure.

Purpose of the Study:

• To evaluate the utility of plasma cfDNA concentration as a rapid triage biodosimetry tool.
• To assess the correlation between cfDNA levels and radiation dose in a non-human primate model.
• To determine if the cfDNA response to radiation is species-independent.

Main Methods:

• Measured cfDNA concentrations in Rhesus macaque plasma using a branched DNA (bDNA) assay.
• Monitored cfDNA levels and hematopoietic parameters over 7 days post-irradiation (1-6.5 Gy).
• Compared results with existing mouse models and human Chernobyl data.

Main Results:

• cfDNA concentration increased exponentially with radiation dose.
• Low-dose (0-2 Gy) and high-dose (5.5-6.5 Gy) exposures were clearly distinguishable.
• Fold changes in cfDNA were comparable to human data, suggesting species independence.
• Average cfDNA levels ranged from 50 ng/mL pre-irradiation to 1585 ng/mL at 6.5 Gy.

Conclusions:

• Plasma cfDNA concentration serves as a reliable biodosimetry marker for radiation exposure.
• The cfDNA response to radiation appears conserved across species, supporting a common mechanism.
• This assay, available in CLIA-ready form, offers a promising tool for rapid triage, though further refinement is needed.