Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice Journal Article
| Authors: | Paris, F.; Fuks, Z.; Kang, A.; Capodieci, P.; Juan, G.; Ehleiter, D.; Haimovitz-Friedman, A.; Cordon-Cardo, C.; Kolesnick, R. |
| Article Title: | Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice |
| 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 Lieberkühn 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. |
| Keywords: | controlled study; gene deletion; pathogenesis; nonhuman; chemotherapy; neoplasms; mouse; animals; mice; apoptosis; genes; gene expression; bone marrow; animal experiment; animal model; radiation injury; oncology; mice, inbred c57bl; animalia; endothelium, vascular; ionizing radiation; tumor suppressor protein p53; stem cells; bone marrow transplantation; intestines; fibroblast growth factor; fibroblast growth factors; intestine injury; whole-body irradiation; sphingomyelin phosphodiesterase; cells; in situ nick-end labeling; intestinal mucosa; radiation damage; crypt cell; annexin a5; capillaries; receptors, fibroblast growth factor; humans; priority journal; article; endothelium lesion |
| Journal Title: | Science |
| Volume: | 293 |
| Issue: | 5528 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2001-07-13 |
| Start Page: | 293 |
| End Page: | 297 |
| Language: | English |
| DOI: | 10.1126/science.1060191 |
| PUBMED: | 11452123 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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