p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/84638 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0002-7994-7963 |
| _version_ | 1826206057007939584 |
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| author | Kirsch, David G. Santiago, Philip M. di Tomaso, Emmanuelle Sullivan, Julie M. Hou, Wu-Shiun Dayton, Talya Lucia Jeffords, Laura B. Sodha, Pooja Mercer, Kim L. Cohen, Rhianna Takeuchi, Osamu Korsmeyer, Stanley J. Bronson, Roderick T. Kim, Carla F. Haigis, Kevin M. Jain, Rakesh K. Jacks, Tyler E |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kirsch, David G. Santiago, Philip M. di Tomaso, Emmanuelle Sullivan, Julie M. Hou, Wu-Shiun Dayton, Talya Lucia Jeffords, Laura B. Sodha, Pooja Mercer, Kim L. Cohen, Rhianna Takeuchi, Osamu Korsmeyer, Stanley J. Bronson, Roderick T. Kim, Carla F. Haigis, Kevin M. Jain, Rakesh K. Jacks, Tyler E |
| author_sort | Kirsch, David G. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:23:24Z |
| format | Article |
| id | mit-1721.1/84638 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:23:24Z |
| publishDate | 2014 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/846382022-09-28T13:48:38Z p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis Kirsch, David G. Santiago, Philip M. di Tomaso, Emmanuelle Sullivan, Julie M. Hou, Wu-Shiun Dayton, Talya Lucia Jeffords, Laura B. Sodha, Pooja Mercer, Kim L. Cohen, Rhianna Takeuchi, Osamu Korsmeyer, Stanley J. Bronson, Roderick T. Kim, Carla F. Haigis, Kevin M. Jain, Rakesh K. Jacks, Tyler E Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Kirsch, David G. Santiago, Philip M. Hou, Wu-Shiun Dayton, Talya Lucia Sodha, Pooja Mercer, Kim L. Cohen, Rhianna Kim, Carla F. Haigis, Kevin M. Jacks, Tyler E. 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. Howard Hughes Medical Institute National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051) National Cancer Institute (U.S.) (Grant K08 CA 114176) Dana-Farber Cancer Institute (Medical Countermeasures Against Radiation Pilot Project U19-AI06775) National Institute of Allergy and Infectious Diseases (U.S.) (Grant RC1-AI078521) American Society of Clinical Oncology (Young Investigator Award) 2014-02-03T13:57:09Z 2014-02-03T13:57:09Z 2009-12 2008-09 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/84638 Kirsch, D. G., P. M. Santiago, E. di Tomaso, J. M. Sullivan, W.-S. Hou, T. Dayton, L. B. Jeffords, et al. “p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis.” Science 327, no. 5965 (January 28, 2010): 593-596. https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0002-7994-7963 en_US http://dx.doi.org/10.1126/science.1166202 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Kirsch, David G. Santiago, Philip M. di Tomaso, Emmanuelle Sullivan, Julie M. Hou, Wu-Shiun Dayton, Talya Lucia Jeffords, Laura B. Sodha, Pooja Mercer, Kim L. Cohen, Rhianna Takeuchi, Osamu Korsmeyer, Stanley J. Bronson, Roderick T. Kim, Carla F. Haigis, Kevin M. Jain, Rakesh K. Jacks, Tyler E p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis |
| title | p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis |
| title_full | p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis |
| title_fullStr | p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis |
| title_full_unstemmed | p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis |
| title_short | p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis |
| title_sort | p53 controls radiation induced gastrointestinal syndrome in mice independent of apoptosis |
| url | http://hdl.handle.net/1721.1/84638 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0002-7994-7963 |
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