Murine Plasma Structural Lipid Isomers Enable Acute Radiation Dose Stratification

Profiling unsaturated lipid structures in murine blood plasma has identified specific carbon–carbon double bond location isomers that can classify acute radiation doses. In a study applying structural lipidomics to acute radiation assessment, researchers found that resolving double bond positions across plasma lipids provides measurable biomarkers capable of stratifying radiation exposure levels in mice.

Rapid and early radiation biodosimetry remains essential for medical triage and clinical intervention following suspected radiation exposure. Although lipids are recognized as promising biodosimetry candidates due to their high radiosensitivity, radiation-induced structural alterations—specifically shifts among carbon–carbon double bond location isomers—have historically remained poorly characterized. To address this, the investigators combined the Paternò-Büchi photochemical reaction with liquid chromatography-tandem mass spectrometry to quantify unsaturated isomers while minimizing interindividual variation.

Using the coupled chromatography and mass spectrometry platform, the team resolved 83 species-level lipids and 311 carbon–carbon double bond location isomers within two major phospholipid classes: phosphatidylcholine and phosphatidylethanolamine. These comprehensive plasma profiles established the structural catalog used to evaluate dose-dependent lipid alterations.

To identify the most informative biomarkers for dose prediction, the researchers applied least absolute shrinkage and selection operator regression to the profiling dataset. The selection procedure isolated 11 location isomers at the 4-hour mark and 8 lipids at the 24-hour mark. These selected markers were subsequently utilized to construct multivariate regression models, which the investigators refined into optimized three-feature biodosimetry panels validated through receiver operating characteristic analysis curves and bootstrap optimism correction.

The resulting three-feature biodosimetry models achieved strong predictive performance across both male and female cohorts. The statistical models demonstrated an R-squared value greater than 0.8 and yielded optimism-corrected area under the receiver operating characteristic curve values ranging from 0.8224 to 1.0000, confirming consistent dose classification performance regardless of sex.

Beyond statistical classification, the study examined the biological mechanisms underlying the observed lipid shifts through Kyoto Encyclopedia of Genes and Genomes pathway analysis, quantitative real-time polymerase chain reaction, Western blotting, and public transcriptomic datasets. Profiling of the Δ9 monounsaturated isomer together with pathway analysis indicated a dysregulation in cellular fatty acid desaturation, which was accompanied by a measurable reduction in stearoyl-CoA desaturase 1 expression in cultured AHH-1 cells as well as in the blood and bone marrow of irradiated mice.

The authors concluded that carbon–carbon double bond location isomers display favorable dose-classification performance in murine plasma, establishing a technical framework for translational biodosimetry. Because the reported findings derive from murine models and in vitro cell culture, further translational validation will be required before these isomeric lipid panels can inform clinical triage protocols.

The methodological significance of the work rests on introducing structural lipidomics into acute radiation dose assessment for the first time. By employing the photochemical Paternò-Büchi reaction alongside tandem mass spectrometry, the researchers pinpointed double-bond coordinates that exhibit minimal baseline differences between individual subjects.

Finally, the derivation of optimized three-feature models demonstrates the feasibility of practical biodosimetric screening. High-dimensional profiling identified hundreds of candidate structures across phosphatidylcholine and phosphatidylethanolamine classes, yet robust dose stratification was achieved using only three key markers. Because these streamlined models sustained high predictive performance under rigorous bootstrap optimism correction, they illustrate that comprehensive structural lipidomics can be distilled into compact, high-performing diagnostic signatures suitable for translational radiation monitoring.

Subject of Research: Murine plasma structural lipidomics for acute radiation biodosimetry

Article Title: Structural lipidomics identifies murine plasma C=C location isomers for radiation dose stratification

Article References: Yang, R., Song, M., Liu, Q., Tang, J., Wei, Y., Ge, D., Qian, K., Shao, Y., Zhang, H., Xue, H., Liu, Y., Dou, L., & Liu, D. (2026). Structural lipidomics identifies murine plasma C=C location isomers for radiation dose stratification. Cell Biology and Toxicology. https://doi.org/10.1007/s10565-026-10257-1

Image Credits: AI Generated

DOI: 10.1007/s10565-026-10257-1

Keywords: Structural lipidomics, Radiation biodosimetry, C=C location isomers, Paternò-Büchi reaction, LC-PB-MS/MS, Phosphatidylcholine, Phosphatidylethanolamine, C57BL/6 mice, LASSO regression, Stearoyl-CoA desaturase 1, AHH-1 cells, Acute radiation exposure, Dose stratification, Fatty acid desaturation, Δ9 monounsaturated isomer, Receiver operating characteristic, Bootstrap optimism correction, Bone marrow