Citrulline: a physiologic marker enabling quantitation and monitoring of epithelial radiation-induced small bowel damage

Int J Radiat Oncol Biol Phys. 2003 Nov 15;57(4):1067-74. doi: 10.1016/s0360-3016(03)00781-8.


Purpose: 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 and materials: 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.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Citrulline / blood*
  • Female
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / radiation effects
  • Intestine, Small / pathology
  • Intestine, Small / radiation effects*
  • Jejunum / physiology
  • Jejunum / radiation effects
  • Mice
  • Radiation Injuries, Experimental / blood*
  • Radiation Injuries, Experimental / pathology
  • Regeneration
  • Whole-Body Irradiation


  • Biomarkers
  • Citrulline