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Sensitization of Vascular Endothelial Cells to Ionizing Radiation Promotes the Development of Delayed Intestinal Injury in Mice.

Authors
  • Lee, Chang-Lung1, 2
  • Daniel, Andrea R1
  • Holbrook, Matt3
  • Brownstein, Jeremy1
  • Silva Campos, Lorraine Da1
  • Hasapis, Stephanie1
  • Ma, Yan1
  • Borst, Luke B4
  • Badea, Cristian T3
  • Kirsch, David G1, 5
  • 1 Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710.
  • 2 Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
  • 3 Department of Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.
  • 4 Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606.
  • 5 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710.
Type
Published Article
Journal
Radiation Research
Publisher
BioOne (Radiation Research Society)
Publication Date
Sep 01, 2019
Volume
192
Issue
3
Pages
258–266
Identifiers
DOI: 10.1667/RR15371.1
PMID: 31265788
Source
Medline
Language
English
License
Unknown

Abstract

Exposure of the gastrointestinal (GI) tract to ionizing radiation can cause acute and delayed injury. However, critical cellular targets that regulate the development of radiation-induced GI injury remain incompletely understood. Here, we investigated the role of vascular endothelial cells in controlling acute and delayed GI injury after total-abdominal irradiation (TAI). To address this, we used genetically engineered mice in which endothelial cells are sensitized to radiation due to the deletion of the tumor suppressor p53. Remarkably, we found that VE-cadherin-Cre; p53FL/FL mice, in which both alleles of p53 are deleted in endothelial cells, were not sensitized to the acute GI radiation syndrome, but these mice were highly susceptible to delayed radiation enteropathy. Histological examination indicated that VE-cadherin-Cre; p53FL/FL mice that developed delayed radiation enteropathy had severe vascular injury in the small intestine, which was manifested by hemorrhage, loss of microvessels and tissue hypoxia. In addition, using dual-energy CT imaging, we showed that VE-cadherin-Cre; p53FL/FL mice had a significant increase in vascular permeability of the small intestine in vivo 28 days after TAI. Together, these findings demonstrate that while sensitization of endothelial cells to radiation does not exacerbate the acute GI radiation syndrome, it is sufficient to promote the development of late radiation enteropathy.

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