title: 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.
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Kirsch
authors.forename: Philip M
authors.initials: PM
authors.lastname: Santiago
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: di Tomaso
authors.forename: Julie M
authors.initials: JM
authors.lastname: Sullivan
authors.forename: Wu-Shiun
authors.initials: WS
authors.lastname: Hou
authors.forename: Talya
authors.initials: T
authors.lastname: Dayton
authors.forename: Laura B
authors.initials: LB
authors.lastname: Jeffords
authors.forename: Pooja
authors.initials: P
authors.lastname: Sodha
authors.forename: Kim L
authors.initials: KL
authors.lastname: Mercer
authors.forename: Rhianna
authors.initials: R
authors.lastname: Cohen
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Korsmeyer
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Carla F
authors.initials: CF
authors.lastname: Kim
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Haigis
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects*; D017353:Gene Deletion; D016158:Genes, p53; D007410:Intestinal Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein