China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing, P.R. China.
Hubei Center for Disease Control and Prevention, Hubei, P.R. China.
Int J Radiat Biol. 2024;100(10):1481-1492. doi: 10.1080/09553002.2024.2387054. Epub 2024 Aug 13.
Lipidomics is an important tool for triaging exposed individuals, and helps early adoption of prevention and control strategies. The purpose of this study was to screen significantly perturbed lipids between pre- and post-irradiation of human plasma samples after total body irradiation (TBI) and explore potential radiation biomarkers for early radiation classification.
Plasma samples were collected before and after irradiation from 22 hospitalized cases of acute myeloid leukemia (AML) prepared for bone marrow transplantation. Acute total-body γ irradiation was performed at doses of 0, 4, 8, and 12 Gy. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with multiple reaction monitoring (MRM) method was utilized. Self-paired studies before and after irradiation were performed to screen potential lipid categorization markers and markers of dose-response relationships for radiation perturbation in humans. Based on the screened potential markers, a human TBI dose estimation model was developed.
In total, 426 individual lipids from 14 major classes were quantified and 152 potential biomarkers with categorical characteristics were screened. A total of 80 lipids (32 TGs, 29 SMs, 9 FAs, 5 CEs, 5 PIs) were upregulated at 4 Gy, and a total of 91 lipids (39 SMs, 18 TGs, 15 HexCers, 7 CEs, 6 Cers, 3 LacCers, 2 LPEs, 1 PI) were upregulated at 12 Gy. Comparison of the ROC curves between the non-exposed and exposed groups at different doses showed AUC values ranging from 0.807 to 0.876. The metabolic pathways of potential lipid markers are mainly sphingolipid and glycerolipid metabolism, unsaturated fatty acid biosynthesis, fatty acid degradation and biosynthesis. Among the 13 dose-dependent radiosensitive lipids, CE (20:5), CE (18:1) and PI (18:2/18:2) were gradually incorporated into the TBI dose estimation model.
This study suggested that it was feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage. Lipidomics strategies for radiation biodosimetry in humans were established with lipid biomarkers with good dose-response relationship.
脂质组学是筛选暴露个体的重要工具，有助于早期采用预防和控制策略。本研究的目的是筛选全身γ照射（TBI）前后人血浆样本中显著变化的脂质，探索潜在的辐射生物标志物，以进行早期辐射分类。
收集 22 例准备进行骨髓移植的急性髓系白血病（AML）住院患者照射前后的血浆样本。对患者进行 0、4、8 和 12Gy 的急性全身γ照射。采用超高效液相色谱-串联质谱（UPLC-MS/MS）多反应监测（MRM）法进行分析。对照射前后的自身配对研究进行了筛选，以筛选潜在的脂质分类标志物和人类辐射扰动的剂量反应关系标志物。基于筛选出的潜在标志物，建立了人类 TBI 剂量估算模型。
共定量了 14 大类 426 种个体脂质，筛选出 152 种具有分类特征的潜在生物标志物。在 4Gy 时，共有 32 个甘油三酯（TGs）、29 个鞘脂（SMs）、9 个脂肪酸（FAs）、5 个胆固醇酯（CEs）、5 个磷脂酰肌醇（PIs）上调，在 12Gy 时，共有 39 个 SMs、18 个 TGs、15 个己糖神经酰胺（HexCers）、7 个 CEs、6 个 Cer、3 个乳酰神经酰胺（LacCers）、2 个溶血磷脂酰乙醇胺（LPEs）和 1 个磷酸肌醇（PI）上调。比较不同剂量下非暴露组和暴露组的 ROC 曲线，AUC 值范围为 0.807 至 0.876。潜在脂质标志物的代谢途径主要为鞘脂和甘油磷脂代谢、不饱和脂肪酸生物合成、脂肪酸降解和生物合成。在 13 种剂量依赖性辐射敏感脂质中，CE（20:5）、CE（18:1）和 PI（18:2/18:2）逐渐被纳入 TBI 剂量估算模型。
本研究表明，使用靶向脂质组学平台获取定量脂质生物标志物谱进行快速、高通量的分类是可行的。本研究建立了具有良好剂量反应关系的脂质生物标志物，为人类辐射生物剂量学提供了脂质组学策略。
