title: Citrulline as a Biomarker in the Murine Total-Body Irradiation Model: Correlation of Circulating and Tissue Citrulline to Small Intestine Epithelial Histopathology.
abstract: 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.
authors.affiliation: *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.
authors.forename: Jace W
authors.initials: JW
authors.lastname: Jones
authors.forename: Gregory
authors.initials: G
authors.lastname: Tudor
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Tong
authors.forename: Barry
authors.initials: B
authors.lastname: Katz
authors.forename: Ann M
authors.initials: AM
authors.lastname: Farese
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: MacVittie
authors.forename: Catherine
authors.initials: C
authors.lastname: Booth
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Kane
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000097:blood*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D007410:Intestinal Diseases / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000528:radiation effects; D007421:Intestine, Small / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D002956:Citrulline