Radiation metabolomics. 2. Dose- and time-dependent urinary excretion of deaminated purines and pyrimidines after sublethal gamma-radiation exposure in mice

Tyburski, John B; Patterson, Andrew D; Krausz, Kristopher W; Slavík, Josef; Fornace, Albert J; Gonzalez, Frank J; Idle, Jeffrey R (2009). Radiation metabolomics. 2. Dose- and time-dependent urinary excretion of deaminated purines and pyrimidines after sublethal gamma-radiation exposure in mice. Radiation research, 172(1), pp. 42-57. Lawrence, Kans.: Radiation Research Society 10.1667/RR1703.1

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Gamma-radiation exposure of humans is a major public health concern as the threat of terrorism and potential hostile use of radiological devices increases worldwide. We report here the effects of sublethal gamma-radiation exposure on the mouse urinary metabolome determined using ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry-based metabolomics. Five urinary biomarkers of sublethal radiation exposure that were statistically significantly elevated during the first 24 h after exposure to doses ranging from 1 to 3 Gy were unequivocally identified by tandem mass spectrometry. These are deaminated purine and pyrimidine derivatives, namely, thymidine, 2'-deoxyuridine, 2'-deoxyxanthosine, xanthine and xanthosine. Furthermore, the aminopyrimidine 2'-deoxycytidine appeared to display reduced urinary excretion at 2 and 3 Gy. The elevated biomarkers displayed a time-dependent excretion, peaking in urine at 8-12 h but returning to baseline by 36 h after exposure. It is proposed that 2'-deoxyuridine and 2'-deoxyxanthosine arise as a result of gamma irradiation by nitrosative deamination of 2'-deoxycytidine and 2'-deoxyguanosine, respectively, and that this further leads to increased synthesis of thymidine, xanthine and xanthosine. The urinary excretion of deaminated purines and pyrimidines, at the expense of aminopurines and aminopyrimidines, appears to form the core of the urinary radiation metabolomic signature of mice exposed to sublethal doses of ionizing radiation.

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

ISBN:

19580506

Publisher:

Radiation Research Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:07

Last Modified:

06 Dec 2013 13:55

Publisher DOI:

10.1667/RR1703.1

PubMed ID:

19580506

Web of Science ID:

000267619200005

URI:

https://boris.unibe.ch/id/eprint/29606 (FactScience: 153899)

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