Lipidomics of longer-term effects in the murine model after exposure to mixed field radiation and combined infection.

BACKGROUND

Accurate biodosimetry is essential for medical response during nuclear emergencies. However, mixed-field radiation and secondary infections create significant diagnostic challenges.

OBJECTIVE

This study aimed to characterize persistent serum lipidomic alterations following mixed-field exposures at long-term time points and evaluate the impact of a delayed secondary infection on radiation-associated signatures to determine the feasibility of serum biomarkers for complex biodosimetry.

METHODS

Target serum lipidomics and untargeted metabolomics were performed on male C57BL/6 mice 6 weeks after a 3 Gy total body irradiation (TBI) with X rays or mixed γ-ray/neutron fields (5%-80% neutron fractions). A subset modeled secondary complications via a delayed Listeria monocytogenes (Lm-OVA) infection at 5 weeks post-TBI.

RESULTS

Mixed-field exposures produced significant, quality-dependent reductions in mitochondrial cardiolipins (CL) and ether-linked phosphatidylethanolamines (ePEs) compared to sham or X ray groups. Untargeted analysis identified that Lm-OVA infection introduced massive systemic metabolic variation. Targeted profiling revealed that while infection alone significantly reduced ceramide and hexosylceramide levels, irradiated and infected mice exhibited profiles resembling irradiated-only animals, suggesting radiation-induced immune suppression attenuates infection-driven lipid remodeling.

CONCLUSION

Radiation quality drives distinct, long-term serum lipidomic signatures that post-exposure infection modulates but does not override. These findings support the advancement of circulating lipids as mechanistically informative biomarkers and the feasibility of serum lipidomics for multiplex biomarker panels in emergency preparedness.