Abstract
Purpose: 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.
Materials and methods: 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.
Results: 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.
Conclusions: 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.
Acknowledgements
The authors wish to thank Professor Bernhard Lauterburg in Bern for his support of this work and helpful discussions and Hans Sägesser for producing the stainless steel cradle for collection of rat sebum. This work was performed as part of the Columbia University Center for Medical Countermeasures against Radiation (P.I. David Brenner) and funded by NIH (NIAID) grant U19 AI067773-05/-06. JRI is grateful to U.S. Smokeless Tobacco Company for a grant for collaborative research.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.