Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Endothelium, Vascular
  • Intestinal Mucosa
  • Intestines

abstract

  • Gastrointestinal (GI) tract damage by chemotherapy or radiation limits their efficacy in cancer treatment. Radiation has been postulated to target epithelial stem cells within the crypts of Lieberk├╝hn to initiate the lethal GI syndrome. Here, we show in mouse models that microvascular endothelial apoptosis is the primary lesion leading to stem cell dysfunction. Radiation-induced crypt damage, organ failure, and death from the GI syndrome were prevented when endothelial apoptosis was inhibited pharmacologically by intravenous basic fibroblast growth factor (bFGF) or genetically by deletion of the acid sphingomyelinase gene. Endothelial, but not crypt, cells express FGF receptor transcripts, suggesting that the endothelial lesion occurs before crypt stem cell damage in the evolution of the GI syndrome. This study provides a basis for new approaches to prevent radiation damage to the bowel.

publication date

  • July 13, 2001

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.1060191

PubMed ID

  • 11452123

Additional Document Info

start page

  • 293

end page

  • 7

volume

  • 293

number

  • 5528