Document Detail


Ionizing radiation is a potent inducer of mitotic recombination in mouse embryonic stem cells.
MedLine Citation:
PMID:  21802432     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Maintenance of genomic integrity in embryonic cells is pivotal to proper embryogenesis, organogenesis and to the continuity of species. Cultured mouse embryonic stem cells (mESCs), a model for early embryonic cells, differ from cultured somatic cells in their capacity to remodel chromatin, in their repertoire of DNA repair enzymes, and in the regulation of cell cycle checkpoints. Using 129XC3HF1 mESCs heterozygous for Aprt, we characterized loss of Aprt heterozygosity after exposure to ionizing radiation. We report here that the frequency of loss of heterozygosity mutants in mESCs can be induced several hundred-fold by exposure to 5-10Gy of X-rays. This induction is 50-100-fold higher than the induction reported for mouse adult or embryonic fibroblasts. The primary mechanism underlying the elevated loss of heterozygosity after irradiation is mitotic recombination, with lesser contributions from deletions and gene conversions that span Aprt. Aprt point mutations and epigenetic inactivation are very rare in mESCs compared to fibroblasts. Mouse ESCs, therefore, are distinctive in their response to ionizing radiation and studies of differentiated cells may underestimate the mutagenic effects of ionizing radiation on ESC or other stem cells. Our findings are important to understanding the biological effects of ionizing radiation on early development and carcinogenesis.
Authors:
Natalia G Denissova; Irina V Tereshchenko; Eric Cui; Peter J Stambrook; Changshun Shao; Jay A Tischfield
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-23
Journal Detail:
Title:  Mutation research     Volume:  715     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-13     Completed Date:  2011-11-22     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
Copyright Information:
2011 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adenine Phosphoribosyltransferase / genetics
Animals
Cell Line
DNA Repair Enzymes / metabolism
Embryonic Stem Cells / radiation effects*
Loss of Heterozygosity / radiation effects*
Mice
Mice, Inbred C57BL
Mutation
Point Mutation
Radiation, Ionizing*
Recombination, Genetic / radiation effects*
Grant Support
ID/Acronym/Agency:
1R01ES012695/ES/NIEHS NIH HHS; 2P30ES006096-16A1/ES/NIEHS NIH HHS; 5R01ES012695-03/ES/NIEHS NIH HHS; R01 ES011633/ES/NIEHS NIH HHS; R01 ES011633-01/ES/NIEHS NIH HHS; R01 ES011633-02/ES/NIEHS NIH HHS; R01 ES011633-03/ES/NIEHS NIH HHS; R01 ES011633-04/ES/NIEHS NIH HHS; R01 ES011633-05/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
EC 2.4.2.7/Adenine Phosphoribosyltransferase; EC 6.5.1.-/DNA Repair Enzymes
Comments/Corrections

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