PMID- 20019247
OWN - NLM
STAT- MEDLINE
DCOM- 20100217
LR  - 20220318
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 327
IP  - 5965
DP  - 2010 Jan 29
TI  - p53 controls radiation-induced gastrointestinal syndrome in mice independent of 
      apoptosis.
PG  - 593-6
LID - 10.1126/science.1166202 [doi]
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 
      apoptosis.
FAU - Kirsch, David G
AU  - Kirsch DG
AD  - David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute 
      of Technology, Cambridge, MA 02139, USA.
FAU - Santiago, Philip M
AU  - Santiago PM
FAU - di Tomaso, Emmanuelle
AU  - di Tomaso E
FAU - Sullivan, Julie M
AU  - Sullivan JM
FAU - Hou, Wu-Shiun
AU  - Hou WS
FAU - Dayton, Talya
AU  - Dayton T
FAU - Jeffords, Laura B
AU  - Jeffords LB
FAU - Sodha, Pooja
AU  - Sodha P
FAU - Mercer, Kim L
AU  - Mercer KL
FAU - Cohen, Rhianna
AU  - Cohen R
FAU - Takeuchi, Osamu
AU  - Takeuchi O
FAU - Korsmeyer, Stanley J
AU  - Korsmeyer SJ
FAU - Bronson, Roderick T
AU  - Bronson RT
FAU - Kim, Carla F
AU  - Kim CF
FAU - Haigis, Kevin M
AU  - Haigis KM
FAU - Jain, Rakesh K
AU  - Jain RK
FAU - Jacks, Tyler
AU  - Jacks T
LA  - eng
GR  - K08 CA114176/CA/NCI NIH HHS/United States
GR  - RC1-AI078521/AI/NIAID NIH HHS/United States
GR  - RC1 AI078521-01/AI/NIAID NIH HHS/United States
GR  - U19-AI06775/AI/NIAID NIH HHS/United States
GR  - P30 CA014051/CA/NCI NIH HHS/United States
GR  - P30-CA14051/CA/NCI NIH HHS/United States
GR  - P01 CA080124/CA/NCI NIH HHS/United States
GR  - P01 CA80124/CA/NCI NIH HHS/United States
GR  - P01 CA080124-01A1/CA/NCI NIH HHS/United States
GR  - P30 CA014051-38/CA/NCI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - K08 CA 114176/CA/NCI NIH HHS/United States
GR  - K08 CA114176-05/CA/NCI NIH HHS/United States
GR  - RC1 AI078521/AI/NIAID NIH HHS/United States
GR  - P30 DK043351/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091217
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Bak1 protein, mouse)
RN  - 0 (Bax protein, mouse)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (bcl-2-Associated X Protein)
SB  - IM
EIN - Science. 2011 Nov 11;334(6057):761
MH  - Animals
MH  - *Apoptosis
MH  - Cell Death
MH  - Epithelial Cells/cytology/physiology/radiation effects
MH  - Gamma Rays/*adverse effects
MH  - Gene Deletion
MH  - Genes, p53
MH  - Intestinal Diseases/etiology/pathology/*physiopathology
MH  - Intestinal Mucosa/pathology/physiopathology/*radiation effects
MH  - Intestine, Small/pathology/physiopathology/*radiation effects
MH  - Mesoderm/cytology
MH  - Mice
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Radiation Dosage
MH  - Radiation Injuries/etiology/pathology/*physiopathology
MH  - Tumor Suppressor Protein p53/*physiology
MH  - bcl-2 Homologous Antagonist-Killer Protein/genetics/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
PMC - PMC2897160
MID - NIHMS178596
EDAT- 2009/12/19 06:00
MHDA- 2010/02/18 06:00
PMCR- 2010/07/29
CRDT- 2009/12/19 06:00
PHST- 2009/12/19 06:00 [entrez]
PHST- 2009/12/19 06:00 [pubmed]
PHST- 2010/02/18 06:00 [medline]
PHST- 2010/07/29 00:00 [pmc-release]
AID - science.1166202 [pii]
AID - 10.1126/science.1166202 [doi]
PST - ppublish
SO  - Science. 2010 Jan 29;327(5965):593-6. doi: 10.1126/science.1166202. Epub 2009 Dec 
      17.