PMID- 22841781
OWN - NLM
STAT- MEDLINE
DCOM- 20130114
LR  - 20220316
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 143
IP  - 5
DP  - 2012 Nov
TI  - Crypt base columnar stem cells in small intestines of mice are radioresistant.
PG  - 1266-1276
LID - S0016-5085(12)01131-6 [pii]
LID - 10.1053/j.gastro.2012.07.106 [doi]
AB  - BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and 
      radiation resistant, repairing DNA double-strand breaks by nonhomologous end 
      joining. However, the population of putative small intestinal stem cells (ISCs) 
      at position +4 from the crypt base contradicts this model, in that they are 
      highly radiosensitive. Cycling crypt base columnar cells (CBCs) at crypt 
      positions +1-3 recently were defined as an alternative population of ISCs. Little 
      is known about the sensitivity of this stem cell population to radiation. 
      METHODS: Radiation-induced lethality of CBCs was quantified kinetically in 
      Lgr5-lacZ transgenic mice. gamma-H2AX, BRCA1, RAD51, and DNA-PKcs foci were used as 
      DNA repair surrogates to investigate the inherent ability of CBCs to recognize 
      and repair double-strand breaks. 5-ethynyl-2'-deoxyuridine and 
      5-bromo-2'-deoxyuridine incorporation assays were used to study patterns of CBC 
      growth arrest and re-initiation of cell cycling. Apoptosis was evaluated by 
      caspase-3 staining. RESULTS: CBCs are relatively radioresistant, repairing DNA by 
      homologous recombination significantly more efficiently than transit amplifying 
      progenitors or villus cells. CBCs undergo apoptosis less than 24 hours after 
      irradiation (32% +/- 2% of total lethality) or mitotic death at 24-48 hours. 
      Survival of CBCs at 2 days predicts crypt regeneration at 3.5 days and lethality 
      from gastrointestinal syndrome. Crypt repopulation originates from CBCs that 
      survive irradiation. CONCLUSIONS: Adult ISCs in mice can cycle rapidly yet still 
      be radioresistant. Importantly, homologous recombination can protect adult stem 
      cell populations from genotoxic stress. These findings broaden and refine 
      concepts of the phenotype of adult stem cells.
CI  - Copyright (c) 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
FAU - Hua, Guoqiang
AU  - Hua G
AD  - Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New 
      York, New York.
FAU - Thin, Tin Htwe
AU  - Thin TH
AD  - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New 
      York, New York.
FAU - Feldman, Regina
AU  - Feldman R
AD  - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New 
      York, New York.
FAU - Haimovitz-Friedman, Adriana
AU  - Haimovitz-Friedman A
AD  - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New 
      York, New York.
FAU - Clevers, Hans
AU  - Clevers H
AD  - Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 
      3584CT Utrecht, The Netherlands.
FAU - Fuks, Zvi
AU  - Fuks Z
AD  - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New 
      York, New York.
FAU - Kolesnick, Richard
AU  - Kolesnick R
AD  - Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New 
      York, New York. Electronic address: r-kolesnick@ski.mskcc.org.
LA  - eng
GR  - R01 CA105125/CA/NCI NIH HHS/United States
GR  - R01#CA105125/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120727
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
SB  - IM
CIN - Gastroenterology. 2012 Nov;143(5):1144-1147. doi: 10.1053/j.gastro.2012.09.021. 
      PMID: 23000480
MH  - Adult Stem Cells/*radiation effects
MH  - Animals
MH  - Apoptosis/radiation effects
MH  - Bone Marrow/radiation effects
MH  - Cell Cycle Checkpoints/radiation effects
MH  - DNA Breaks, Double-Stranded/*radiation effects
MH  - *DNA Repair
MH  - Jejunum/pathology/*radiation effects
MH  - Mice
MH  - Mice, Transgenic
MH  - *Radiation Tolerance
PMC - PMC3480544
MID - NIHMS398559
EDAT- 2012/07/31 06:00
MHDA- 2013/01/15 06:00
PMCR- 2013/11/01
CRDT- 2012/07/31 06:00
PHST- 2011/09/29 00:00 [received]
PHST- 2012/06/22 00:00 [revised]
PHST- 2012/07/15 00:00 [accepted]
PHST- 2012/07/31 06:00 [entrez]
PHST- 2012/07/31 06:00 [pubmed]
PHST- 2013/01/15 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - S0016-5085(12)01131-6 [pii]
AID - 10.1053/j.gastro.2012.07.106 [doi]
PST - ppublish
SO  - Gastroenterology. 2012 Nov;143(5):1266-1276. doi: 10.1053/j.gastro.2012.07.106. 
      Epub 2012 Jul 27.