Institute of Clinical Pharmacology and Visceral Research, University of Bern, Bern, Switzerland.
Int J Radiat Biol. 2011 Apr;87(4):360-71. doi: 10.3109/09553002.2010.537432. Epub 2010 Dec 15.
The aim of this work was to use metabolomics to evaluate sebum as a source of biomarkers for gamma-radiation exposure in the rat, and potentially in man. Proof of concept of radiation metabolomics was previously demonstrated in both mouse and rat urine, from the radiation dose- and time-dependent excretion of a set of urinary biomarkers.
Rats were gamma-irradiated (3 Gy) or sham irradiated and groups of rats were euthanised at 1 h or 24 h post-irradiation. Sebum was collected by multiple washings of the carcasses with acetone. Nonpolar lipids were extracted, methylated, separated and quantitated using gas chromatography-mass spectrometry (GCMS). Metabolomic analysis of the GCMS data was performed using both orthogonal projection to latent structures-discriminant analysis and random forests machine learning algorithm.
Irradiation did not alter sebum production. A total of 35 lipids were identified in rat sebum, 29 fatty acids, five fatty aldehydes, and cholesterol. Metabolomics showed that three fatty acids, palmitic, 2-hydroxypalmitic, and stearic acids were potential biomarkers. Sebaceous palmitic acid was marginally statistically significantly elevated (7.5-8.4%) at 24 h post-irradiation.
Rat sebaceous gland appears refractory to 3 Gy gamma-irradiation. Unfortunately, collection of sebum shortly after gamma-irradiation is unlikely to form the basis of high-throughput non-invasive radiation biodosimetry in man.
本研究旨在利用代谢组学技术,评估皮脂作为大鼠(以及人类)γ 射线暴露生物标志物的来源。此前,在小鼠和大鼠尿液中,通过一组尿液生物标志物的辐射剂量和时间依赖性排泄,已经证明了辐射代谢组学的概念验证。
大鼠接受γ 射线照射(3 Gy)或假照射,照射后 1 小时或 24 小时处死一组大鼠。用丙酮多次洗涤尸体收集皮脂。采用气相色谱-质谱联用仪(GCMS)提取、甲基化、分离和定量非极性脂质。使用正交投影到潜在结构判别分析(OPLS-DA)和随机森林机器学习算法对 GCMS 数据进行代谢组学分析。
照射并未改变皮脂的产生。在大鼠皮脂中鉴定出 35 种脂质,包括 29 种脂肪酸、5 种脂肪醛和胆固醇。代谢组学显示,三种脂肪酸,棕榈酸、2-羟棕榈酸和硬脂酸可能是潜在的生物标志物。照射后 24 小时,皮脂中的棕榈酸略有统计学意义上的升高(7.5-8.4%)。
大鼠皮脂腺对 3 Gy γ 射线照射具有抗辐射性。不幸的是,在 γ 射线照射后不久采集皮脂不太可能成为人类高通量非侵入性辐射生物剂量测定的基础。