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

Lee, Chang-Lung

Daniel, Andrea R

Holbrook, Matt

Brownstein, Jeremy

Silva Campos, Lorraine Da

Hasapis, Stephanie

Ma, Yan

Borst, Luke B

Badea, Cristian T

Kirsch, David G

2021-08-09T13:21:54Z

2021-08-09T13:21:54Z

2019-09

2021-08-09T13:21:52Z

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; p53^FL/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; p53^FL/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; p53^FL/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.

10.1667/RR15371.1

0033-7587

1938-5404

https://hdl.handle.net/10161/23576

eng

Radiation Research Society

Radiation research

10.1667/rr15371.1

Intestines

Endothelial Cells

Animals

Mice

Cell Hypoxia

Gene Deletion

Capillary Permeability

Radiation Tolerance

Time Factors

Tumor Suppressor Protein p53

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

Journal article

Lee, Chang-Lung|0000-0002-0673-633X

Badea, Cristian T|0000-0002-1850-2522

258

266

3

School of Medicine

Biomedical Engineering

Duke Cancer Institute

Radiology

Duke

Pratt School of Engineering

Institutes and Centers

Clinical Science Departments

Pharmacology & Cancer Biology

Radiation Oncology

Basic Science Departments

Pathology

Published

192