115 The influence of 5-fluorouracil on the appearance of endothelium in small arteries. A scanning and transmission electron microscopic study in rabbits

Cardiotoxicity of 5-ftuorouracil (5-FU) is mysterious toxic manifestation in treatment of human malignancies. Its possible mechanism might be direct cytotoxic effect on endothelium in cardiac vessels. We tested this hypothesis in experimental study in rabbits. The small arteries after in vivo treatment with 5-FU were prepared by perfusion-fixation method. Scanning and transmission electron microscopy evaluation of endothelium was done. We found irreversible cell damage consisting of disruption of endothelium sheet and patchy exposure of subendothelium, frequently observed as location fur thrombus furmation. Findings support the hypothesis about the thrombogenic effect of 5-FU, secondary to its direct cytotoxic effect on endothelium as pathophysiological mechanism behind 5-FU cardiotoxicity.