» Articles » PMID: 20019247

P53 Controls Radiation-induced Gastrointestinal Syndrome in Mice Independent of Apoptosis

Abstract

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.

Citing Articles

STING directly interacts with PAR to promote apoptosis upon acute ionizing radiation-mediated DNA damage.

Sun Y, Aliyari S, Parvatiyar K, Wang L, Zhen A, Sun W Cell Death Differ. 2025; .

PMID: 39939798 DOI: 10.1038/s41418-025-01457-z.


Mutant p53 regulates a distinct gene set by a mode of genome occupancy that is shared with wild type.

Rahme R, Resnick-Silverman L, Anguiano V, Campbell M, Fenaux P, Manfredi J EMBO Rep. 2025; 26(5):1315-1343.

PMID: 39875582 PMC: 11893899. DOI: 10.1038/s44319-025-00375-y.


A comprehensive review of sensors of radiation-induced damage, radiation-induced proximal events, and cell death.

Saini S, Gurung P Immunol Rev. 2024; 329(1):e13409.

PMID: 39425547 PMC: 11742653. DOI: 10.1111/imr.13409.


Vasoactive intestinal peptide promotes secretory differentiation and mitigates radiation-induced intestinal injury.

Agibalova T, Hempel A, Maurer H, Ragab M, Ermolova A, Wieland J Stem Cell Res Ther. 2024; 15(1):348.

PMID: 39380035 PMC: 11462795. DOI: 10.1186/s13287-024-03958-z.


p53 promotes revival stem cells in the regenerating intestine after severe radiation injury.

Morral C, Ayyaz A, Kuo H, Fink M, Verginadis I, Daniel A Nat Commun. 2024; 15(1):3018.

PMID: 38589357 PMC: 11001929. DOI: 10.1038/s41467-024-47124-8.


References
1.
Christophorou M, Ringshausen I, Finch A, Swigart L, Evan G . The pathological response to DNA damage does not contribute to p53-mediated tumour suppression. Nature. 2006; 443(7108):214-7. DOI: 10.1038/nature05077. View

2.
Qiu W, Carson-Walter E, Liu H, Epperly M, Greenberger J, Zambetti G . PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell. 2008; 2(6):576-83. PMC: 2892934. DOI: 10.1016/j.stem.2008.03.009. View

3.
Mettler Jr F, Voelz G . Major radiation exposure--what to expect and how to respond. N Engl J Med. 2002; 346(20):1554-61. DOI: 10.1056/NEJMra000365. View

4.
Komarova E, Kondratov R, Wang K, Christov K, Golovkina T, Goldblum J . Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice. Oncogene. 2004; 23(19):3265-71. DOI: 10.1038/sj.onc.1207494. View

5.
El Marjou F, Janssen K, Chang B, Li M, Hindie V, Chan L . Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis. 2004; 39(3):186-93. DOI: 10.1002/gene.20042. View