TY - JOUR
T1 - P53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis
AU - Kirsch, David G.
AU - Santiago, Philip M.
AU - Di Tomaso, Emmanuelle
AU - Sullivan, Julie M.
AU - Hou, Wu Shiun
AU - Dayton, Talya
AU - Jeffords, Laura B.
AU - Sodha, Pooja
AU - Mercer, Kim L.
AU - Cohen, Rhianna
AU - Takeuchi, Osamu
AU - Korsmeyer, Stanley J.
AU - Bronson, Roderick T.
AU - Kim, Carla F.
AU - Haigis, Kevin M.
AU - Jain, Rakesh K.
AU - Jacks, Tyler
PY - 2010
Y1 - 2010
N2 - 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 apoptossis.
AB - 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 apoptossis.
UR - http://www.scopus.com/inward/record.url?scp=75749114436&partnerID=8YFLogxK
U2 - 10.1126/science.1166202
DO - 10.1126/science.1166202
M3 - Article
C2 - 20019247
AN - SCOPUS:75749114436
SN - 0036-8075
VL - 327
SP - 593
EP - 596
JO - Science
JF - Science
IS - 5965
ER -