| p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. | |
| | |
MedLine Citation:
|
PMID: 20019247 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Acute exposure to ionizing radiation can cause lethal damage to the gastrointestinal (GI) tract, a condition called the GI syndrome. Whether the target cells affected by radiation to cause the GI syndrome are derived from the epithelium or endothelium and whether the target cells die by apoptosis or other mechanisms are controversial issues. Studying mouse models, we found that selective deletion of the proapoptotic genes Bak1 and Bax from the GI epithelium or from endothelial cells did not protect mice from developing the GI syndrome after sub-total-body gamma irradiation. In contrast, selective deletion of p53 from the GI epithelium, but not from endothelial cells, sensitized irradiated mice to the GI syndrome. Transgenic mice overexpressing p53 in all tissues were protected from the GI syndrome after irradiation. These results suggest that the GI syndrome is caused by the death of GI epithelial cells and that these epithelial cells die by a mechanism that is regulated by p53 but independent of apoptosis. |
| | |
Authors:
|
David G Kirsch; Philip M Santiago; Emmanuelle di Tomaso; Julie M Sullivan; Wu-Shiun Hou; Talya Dayton; Laura B Jeffords; Pooja Sodha; Kim L Mercer; Rhianna Cohen; Osamu Takeuchi; Stanley J Korsmeyer; Roderick T Bronson; Carla F Kim; Kevin M Haigis; Rakesh K Jain; Tyler Jacks |
Related Documents
:
|
2334077 - Peutz-jeghers syndrome. a call for intraoperative enteroscopy. 2867457 - The pharmacotherapy of migraine. 16964417 - Multiple colon carcinomas in a patient with cowden syndrome. 9795507 - Blue rubber bleb nevus syndrome: a cause of gastrointestinal hemorrhage. 8780107 - Acute ventilatory failure in lambert-eaton myasthenic syndrome and its response to 3,4-... 6093987 - The concurrence of saethre-chotzen syndrome and malignancy in a family with in vitro im... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-12-17 |
Journal Detail:
|
Title: Science (New York, N.Y.) Volume: 327 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2010 Jan |
Date Detail:
|
Created Date: 2010-01-29 Completed Date: 2010-02-17 Revised Date: 2011-11-28 |
Medline Journal Info:
|
Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
|
Languages: eng Pagination: 593-6 Citation Subset: IM |
Affiliation:
|
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis* Cell Death Epithelial Cells / cytology, physiology, radiation effects Gamma Rays / adverse effects* Gene Deletion Genes, p53 Intestinal Diseases / etiology, pathology, physiopathology* Intestinal Mucosa / pathology, physiopathology, radiation effects* Intestine, Small / pathology, physiopathology, radiation effects* Mesoderm / cytology Mice Mice, Transgenic Models, Biological Radiation Dosage Radiation Injuries / etiology, pathology, physiopathology* Tumor Suppressor Protein p53 / physiology* bcl-2 Homologous Antagonist-Killer Protein / genetics, metabolism bcl-2-Associated X Protein / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
K08 CA 114176/CA/NCI NIH HHS; K08 CA114176-05/CA/NCI NIH HHS; P01 CA080124-01A1/CA/NCI NIH HHS; P01 CA80124/CA/NCI NIH HHS; P30 CA014051-38/CA/NCI NIH HHS; P30-CA14051/CA/NCI NIH HHS; RC1 AI078521-01/AI/NIAID NIH HHS; RC1-AI078521/AI/NIAID NIH HHS; U19-AI06775/AI/NIAID NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
|
0/Bak1 protein, mouse; 0/Bax protein, mouse; 0/Tumor Suppressor Protein p53; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein |
| Comments/Corrections | |
Erratum In:
|
Science. 2011 Nov 11;334(6057):761 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Metabolism and Excretion of the Novel Bioreductive Prodrug PR-104 in Mice, Rats, Dogs and Humans.
Next Document: Spontaneous and x-ray-triggered crystallization at long range in self-assembling filament networks.