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Citrulline as a Biomarker in the Murine Total-Body Irradiation Model

Correlation of Circulating and Tissue Citrulline to Small Intestine Epithelial Histopathology

Jones, Jace W.*; Tudor, Gregory; Li, Fei*; Tong, Yan; Katz, Barry; Farese, Ann M.§; MacVittie, Thomas J.§; Booth, Catherine; Kane, Maureen A.*

doi: 10.1097/HP.0000000000000346

The use of plasma citrulline as a biomarker for gastrointestinal acute radiation syndrome via exposure to total-body irradiation in a murine model was investigated. The radiation exposure covered lethal, mid-lethal, and sub-lethal gastrointestinal acute radiation syndrome. Plasma citrulline profiles were generated over the first 6 d following total-body irradiation exposure of 6–15 Gy. In addition, plasma citrulline was comprehensively evaluated in the context of matching small intestine citrulline and histopathology. Higher plasma citrulline was significantly associated with lower irradiation doses over the first 6 d following the irradiation insult. Furthermore, higher plasma citrulline was significantly associated with higher crypt survival. The correlation of the plasma citrulline to crypt survival was more robust for higher irradiation doses and for later time points. The data suggested plasma citrulline was most informative for reflecting gastrointestinal injury resulting from exposure to 9–15 Gy total-body irradiation covering time-points 2–5 d post the irradiation insult.

*University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD; †Epistem Ltd, Manchester, UK; ‡Indiana University, School of Medicine and Richard M. Fairbanks School of Public Health, Department of Biostatistics, Indianapolis, IN; §University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.

The authors declare no conflicts of interest.

For correspondence contact: Maureen A. Kane, University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, 20 N. Pine Street, Room 723, Baltimore, MD 21201, or email at

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(Manuscript accepted 24 June 2015)

© 2015 by the Health Physics Society