Radiation metabolomics. 3. Biomarker discovery in the urine of gamma-irradiated rats using a simplified metabolomics protocol of gas chromatography-mass spectrometry combined with random forests machine learning algorithm

Lanz, Christian; Patterson, Andrew D; Slavík, Josef; Krausz, Kristopher W; Ledermann, Monika; Gonzalez, Frank J; Idle, Jeffrey R (2009). Radiation metabolomics. 3. Biomarker discovery in the urine of gamma-irradiated rats using a simplified metabolomics protocol of gas chromatography-mass spectrometry combined with random forests machine learning algorithm. Radiation research, 172(2), pp. 198-212. Lawrence, Kans.: Radiation Research Society 10.1667/RR1796.1

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Abstract Radiation metabolomics employing mass spectral technologies represents a plausible means of high-throughput minimally invasive radiation biodosimetry. A simplified metabolomics protocol is described that employs ubiquitous gas chromatography-mass spectrometry and open source software including random forests machine learning algorithm to uncover latent biomarkers of 3 Gy gamma radiation in rats. Urine was collected from six male Wistar rats and six sham-irradiated controls for 7 days, 4 prior to irradiation and 3 after irradiation. Water and food consumption, urine volume, body weight, and sodium, potassium, calcium, chloride, phosphate and urea excretion showed major effects from exposure to gamma radiation. The metabolomics protocol uncovered several urinary metabolites that were significantly up-regulated (glyoxylate, threonate, thymine, uracil, p-cresol) and down-regulated (citrate, 2-oxoglutarate, adipate, pimelate, suberate, azelaate) as a result of radiation exposure. Thymine and uracil were shown to derive largely from thymidine and 2'-deoxyuridine, which are known radiation biomarkers in the mouse. The radiation metabolomic phenotype in rats appeared to derive from oxidative stress and effects on kidney function. Gas chromatography-mass spectrometry is a promising platform on which to develop the field of radiation metabolomics further and to assist in the design of instrumentation for use in detecting biological consequences of environmental radiation release.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Clinical Pharmacology and Visceral Research [discontinued]

UniBE Contributor:

Idle, Jeffrey

ISSN:

0033-7587

Publisher:

Radiation Research Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:10

Last Modified:

06 Dec 2013 13:57

Publisher DOI:

10.1667/RR1796.1

PubMed ID:

19630524

Web of Science ID:

000268620600006

URI:

https://boris.unibe.ch/id/eprint/30843 (FactScience: 195178)

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