Ultrastructural Studies on Tumor Capillaries of a Rat Rhabdomyosarcoma during Fractionated Radiotherapy

Abstract

Sequential morphological changes in tumor capillaries of isotransplanted R1H rat rhabdomyosarcoma were observed weekly by transmission electron microscopy during fractionated radiotherapy (75 Gy/25 fractions/5 weeks). During the first 2 weeks of irradiation (up to 30 Gy), edema of the tumor capillary wall was induced. Swollen endothelial cells bulged into the vascular lumen and were surrounded by a widened subendothelial space with increased amounts of collagen fibrils (subendothelial edema). The endothelial lining was preserved up to the 3rd week of irradiation (45 Gy). Prolonged irradiation was associated with progressive destruction of the vascular wall including shrinkage, gradual loss of cell contacts, disappearance of the normal chromatin pattern, and increase of cytoplasmic vacuoles in endothelial cells as well as disruption of basal laminae. One week after the end of radiotherapy (75 Gy), the tumor capillaries showed complete necrosis. Progressive damage to tumor capillaries in the course of fractionated radiotherapy might have adverse effects on blood supply and thus on tumor oxygenation.

Impact of Treatment Acceleration and its Timing on the Response of the Rhabdomyosarcoma R1H of the Rat to Fractionated Irradiation

“…For the R1H-tumor an increase of hypoxia as measured using polarographic needle probes and the Eppendorf pO 2 -device with treatment time [24], as well as a severe energy depletion has been described [17]. These changes might be a result of destruction of tumor blood vessels [23] and might also explain the observed decrease of radiosensitivity during fractionated treatment.…”

Enhanced Susceptibility of Irradiated Tumor Vessels to Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibition

“…As the VEGFR TKI in these experiments was given after irradiation, increased radiosensitivity was not the underlying mechanism of this phenomenon. As single radiation doses as well as fractionated irradiation can impair tumor vascularization (26,27), we hypothesized that radiation-damaged tumor vessels are more sensitive to VEGFR TKI than unirradiated tumor vessels. To test this hypothesis in vivo, we investigated FaDu tumors growing in s.c. tissues that were irradiated before tumor transplantation to induce the so-called tumor bed effect (28).…”

Impact of Anemia Prevention by Recombinant Human Erythropoietin on the Sensitivity of Xenografted Glioblastomas to Fractionated Irradiation

“…Several experimental studies have clearly shown that tumor oxygenation is slightly worsened during fractionated irradiation only if the total dose exceeds 45 Gy [40]. The intensified tumor hypoxia in this case is most probably the result of vascular destruction [38,39] followed by a deterioration of nutrient supply [32]. These data may indicate that during fractionated irradiation, the impact of moderate anemia on the oxygenation status of the tumor and, by this, on the radiosensitivity plays only a minor role due to the overwhelming destruction of tumor vasculature.…”