西亚试剂：p53 Controls Radiation-Induced Gastrointestinal Syndrome in

发布时间：2025-06-14

p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis

David G. Kirsch,1,2,3, Philip M. Santiago,1 Emmanuelle di Tomasso,2 Julie M. Sullivan,3 Wu-Shiun Hou,1,Talya Dayton,1 Laura B. Jeffords,3 Pooja Sodha,1 Kim Mercer,1 Rhianna Cohen,1 Osamu Takeuchi,4 Stanley J. Korsmeyer,4,* Roderick Bronson,5 Carla F. Kim,1 Kevin M. Haigis,1,? Rakesh K. Jain,2 Tyler Jacks1,6,

Acute exposure to ionizing radiation can cause lethal damage to the gastrointestinal (GI) tract, a condition called the GI syndrome. Whether the target cells mediating 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 subtotal body gamma irradiation. In contrast, selective deletion of p53 from the GI epithelium, but not 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 death of GI epithelial cells and that these epithelial cells die by a mechanism that is regulated by p53 but independent of apoptosis.

1 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
3 Departments of Radiation Oncology and Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27708, USA.
4 Dana Farber Cancer Institute, Boston, MA 02115, USA.
5 Tufts University School of Medicine and Veterinary Medicine, North Grafton, MA 05136, USA.
6 Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

 

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