Radiation-induced damage in different segments of the rat intestine after external beam irradiation of the liver.

Introduction: The out-of-field effects on the intestine, caused by radiation treatment of a parenchymatous organ, have not previously been studied.

Methods: A single dose of 25Gy was administered percutaneously to the liver of male Wistar rats after a planning CT-scan. Sham-irradiated animals served as controls. At 1, 6, 24, 96h, 1.5 and 3months the duodenum, jejunum, ileum and distal colon were removed, washed and deep-frozen or prepared for paraffin staining.

Results: All animals survived the treatment. Epithelial cell damage occurred in all small-intestinal segments. However, prolonged denudation of the villi together with destruction of the crypt lining was only observed in the ileum, resulting in deficient regeneration. In the colon, changes were minor. Radiation mucositis with granulocyte (MP0+) infiltration was seen from 1 to 24h in the duodenum and jejunum, when ED1+ macrophages, CD3+ T-lymphocytes, and CD34+ hematopoietic precursor cells were recruited, accompanied by an increase in the chemokines MCP-1, MIP-1α, MIP3α and Il-8. In the ileum, early granulocyte infiltration was delayed but continuous. Recruitment of macrophages and lymphocytes was deficient and induction of chemokines as of the adhesion molecules PECAM-1, ICAM-1 was lacking.

Conclusion: Post-irradiation damage to the ileum was delayed and followed by an altered repair process with structural changes of the villi. The observed changes might result from a higher sensitivity to oxidative stress mechanisms with subsequent damage of the regenerative capacity of the crypt-villus axis, accompanied by a sustained "inflammatory response" and vascular damage with a lack of regeneratory cell recruitment.