Endothelial cell death after ionizing radiation does not impair vascular structure. Endothelial cell death after ionizing radiation does not impair vascular structure

The effect of radiation therapy on tumor vasculature has long been a subject of debate. Increased oxygenation and perfusion have been documented during radiation treatments. Conversely, apoptosis of irradiated tumor endothelial cells has been proposed as a major determinant of tumor control. To approach these contradictions, we used multiphoton microscopy in two murine tumor models: MC38, a highly vascularized and B16F10, a moderately vascularized model, grown in transgenic mice with tdTomato labelled endothelium. These tumors received either a single dose of radiation (15 Gy) or a fractionated dose (5x3 Gy). Unexpectedly, even these high doses led to little structural change of the perfused vasculature. However, non-perfused vessels and blind ends were substantially impaired after radiation accompanied by apoptosis of their endothelium. Additionally, proliferation of endothelium was blocked. Further, RNAseq confirmed the modification of gene expression in apoptotic and cell cycle regulation pathways. Therefore, we show that apoptosis of tumor endothelial cells after radiation does not impair vascular structure. Overall design: Bulk and single cell RNA seq are performed on mouse tumor EC without irradiation as control and 48h after irradiation as treatment group.