caa a22 4500 475774248 CHVBK 20180406123626.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1007/s004180000192 doi (NATIONALLICENCE)springer-10.1007/s004180000192 Vascular permeability and hyperpermeability in a murine adenocarcinoma after fractionated radiotherapy: an ultrastructural tracer study [Elektronische Daten] [Paul L. Debbage, Sonja Seidl, Alfons Kreczy, Peter Hutzler, Margit Pavelka, Peter Lukas] Abstract.: Large radiation doses cause postradiation vascular hyperpermeability by disrupting endothelia. The cumulative sequences of small doses (fractionated radiotherapy) standard in clinical practice cause it too, but not by endothelial disruption: the mechanisms are unknown. In this study, correlated fluorescent and ultrastructural localisation of a tracer revealed the architecture, fine structure and function of microvessels in mouse AT17 tumours, before and after 42Gy fractionated radiation. Before irradiation, tumour vascular permeability lay in the normophysiological range defined by the gut and cerebral cortex. A double barrier regulated permeability: vesicular transport through the endothelial wall required approximately 2h and then the basement membrane charge barrier trapped tracer for 2h longer. Irradiation abolished the double barrier: tracer passed instantly through both endothelial wall and underlying basement membrane, forming diffusion haloes around microvessels within 2-5min. Structurally, irradiated tumour microvessels were lined by a continuous and vital endothelium with closed interendothelial junctions; endothelial basement membranes were intact, though loosened. Irradiated endothelia exhibited extremely active membrane motility and intracellular vesicle trafficking. Radiation treatment raised vascular permeability by enhancing transendothelial transcytosis, and by altering the passive filter properties of the subendothelial basement membrane. This type of vascular hyperpermeability should be susceptible to pharmacological modulation. Springer-Verlag, 2000 Tumour Fractionated radiotherapy Vascular permeability Hyperpermeability Lectin tracer Ultrastructure nationallicence Debbage Paul L. Institute of Anatomy and Histology, University of Innsbruck, Müllerstrasse 59, 6020 Innsbruck, Austria aut Seidl Sonja Institute of Anatomy and Histology, University of Innsbruck, Müllerstrasse 59, 6020 Innsbruck, Austria aut Kreczy Alfons Institute of Pathology, University of Innsbruck, Müllerstrasse 44, 6020 Innsbruck, Austria aut Hutzler Peter Department of Pathology, GSF-National Research Centre for Environment and Health, Ingoldstädterstrasse 1, 85758 Oberschleissheim, Germany aut Pavelka Margit Institute of Histology and Embryology, University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria aut Lukas Peter University Clinic for Radiotherapy and Radio-Oncology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria aut https://doi.org/10.1007/s004180000192 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004180000192 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Debbage Paul L. Institute of Anatomy and Histology, University of Innsbruck, Müllerstrasse 59, 6020 Innsbruck, Austria aut NATIONALLICENCE 700 1- Seidl Sonja Institute of Anatomy and Histology, University of Innsbruck, Müllerstrasse 59, 6020 Innsbruck, Austria aut NATIONALLICENCE 700 1- Kreczy Alfons Institute of Pathology, University of Innsbruck, Müllerstrasse 44, 6020 Innsbruck, Austria aut NATIONALLICENCE 700 1- Hutzler Peter Department of Pathology, GSF-National Research Centre for Environment and Health, Ingoldstädterstrasse 1, 85758 Oberschleissheim, Germany aut NATIONALLICENCE 700 1- Pavelka Margit Institute of Histology and Embryology, University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria aut NATIONALLICENCE 700 1- Lukas Peter University Clinic for Radiotherapy and Radio-Oncology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer