Abstracts
2000 Digestive Disease Week

# 2298 Effect of Low-Dose Radiation on the Expression of Intercellular Adhesion Molecule-1 and on the Leukocyte Adherence in Healthy Pancreas and in Pancreatic Carcinoma of the Rat.
Eduard Ryschich, Jan Schmidt, Wolfgang Harms, Jens Werner, Sasa- Marcel Maksan, Martha Maria Gebhard, Christian Herfarth, Ernst Klar, Heidelberg, Germany

Introduction: Leukocyte migration from blood stream into the tissue is controlled by specific adhesion molecules expressed on vascular endothelium. A typical reduction of the expression of adhesion molecules on endothelium of malignant tumor is a possible mechanism which helps the tumors to escape the immune control. Recently, a possible influence of radiation on expression of adhesion molecules in healthy endothelium has been reported. Aims: The aim of the study was to investigate the influence of low dose radiation on the expression of intercellular endothelial adhesion molecule- 1 (ICAM-1) and on leukocyte-endothelium-interaction in healthy pancreas and in pancreatic cancer of the rat. Methods: In 16 male Lewis rats (150-170g) tumor induction of duct-like pancreatic cancer DSL6A was achieved by orthotopic tumor fragment implantation. Local radiation of the pancreas with 5 Gy was performed 6 weeks after tumor implantation. The leukocyte-endothelium-interaction in tumor was investigated 16-18 hours after radiation by intravital microscopy. The number of adherent leukocytes was assessed by computer-assisted image analysis. Labeling of ICAM-1 was performed by standard immunhistochemistry. The expression of adhesion molecules was quantitatively assessed by computer-assisted image analysis and expressed as percent of positive staining compared to the entire surface. Results: The basal expression of ICAM-1 in healthy pancreas was low. The single dose radiation caused a significant increase of the expression of endothelial ICAM-1 in normal pancreas from 0.28±0.16% to 1.66±0.76% (p<0.01). The distinction of endothelial from interstitial ICAM-1 in pancreatic carcinoma was not possible because of high ICAM-1 expression in tumor interstitium. The low-affinity leukocyte adherence in tumor was not significantly increased after radiation. However, the high-affinity leukocyte adherence was significantly increased from 0.68±0.96 sticker/100µm in controls to 3.26±1.15 sticker/100µm after radiation (p=0.01). Conclusions: A local low dose radiation increased the expression of ICAM- 1 and the high-affinity leukocyte-endothelium-interaction in normal and malignant pancreatic tissue. Thus, upregulation of leukocyte adherence by low dose radiation may represent a new approach for the improvement of immunotherapy by cytotoxic T-cells.