Citrulline: a physiologic marker enabling quantitation and monitoring of epithelial radiation-induced small bowel damage.
OBJECTIVE
Small bowel irradiation results in epithelial cell loss and consequently impairs function and metabolism. We investigated whether citrulline, a metabolic end product of small bowel enterocytes, can be used for quantifying radiation-induced epithelial cell loss.


METHODS
NMRI mice were subjected to single-dose whole body irradiation (WBI). The time course of citrullinemia was assessed up to 11 days after WBI. A dose-response relationship was determined at 84 h after WBI. In addition, citrullinemia was correlated with morphologic parameters at this time point and used to calculate the dose-modifying factor (DMF) of glutamine and amifostine on acute small bowel radiation damage.


RESULTS
After WBI, a time- and dose-dependent decrease in plasma citrulline level was observed with a significant dose-response relationship at 84 h. At this time point, citrullinemia significantly correlated with jejunal crypt regeneration (p < 0.001) and epithelial surface lining (p = 0.001). A DMF of 1.0 and 1.5 was computed at the effective dose 50 (ED50) level for glutamine and amifostine, respectively.


CONCLUSIONS
Citrullinemia can be used to quantify acute small bowel epithelial radiation damage after single-dose WBI. Radiation-induced changes in citrullinemia are most pronounced at 3 1/2 to 4 days postirradiation. At this time point, citrullinemia correlates with morphologic endpoints for epithelial radiation damage.
MAASTRO, Department of Radiation Therapy and Oncology, University Hospital Maastricht/Maastricht University, Maastricht, The Netherlands. l.lutgens@rtil.nl
Ludy C H W
LC
Lutgens
Nicolaas E P
NE
Deutz
John
J
Gueulette
Jack P M
JP
Cleutjens
Martijn P F
MP
Berger
Bradly G
BG
Wouters
Maarten F
MF
von Meyenfeldt
Philippe
P
Lambin
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000097:blood*; D005260:Female; D007413:Intestinal Mucosa / Q000473:pathology / Q000528:radiation effects; D007421:Intestine, Small / Q000473:pathology / Q000528:radiation effects*; D007583:Jejunum / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000097:blood* / Q000473:pathology; D012038:Regeneration; D014916:Whole-Body Irradiation
D015415:Biomarkers; D002956:Citrulline