Document Detail


Evidence of genetic instability in 3 Gy X-ray-induced mouse leukaemias and 3 Gy X-irradiated haemopoietic stem cells.
MedLine Citation:
PMID:  11682007     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: If radiation-induced genetic instability is causal in mouse radiation leukaemogenesis, then genetic instability should be detectable in the irradiated target untransformed haemopoietic stem cell, and evidence of genetic instability detected in the clonal radiation-induced leukaemia. We have tested this hypothesis using the CBA/H mouse model of radiation-induced acute myeloid leukaemia (r-AML). MATERIALS AND METHODS: Fluorescence in situ hybridisation (FISH) was employed to screen for chromosomal aberrations in mouse 3 Gy X-ray-induced r-AMLs and in the clonal descendents of control and 3 Gy X-irradiated bone marrow haemopoietic stem cells using the in vitro clonogenic CFU-A colony assay. RESULTS: High levels of clonal non-specific chromosomal aberrations were detected in the r-AML (approximately 4-5 aberrations/r-AML), and ongoing chromosomal instability as defined by subclonal variants detected in 5/10 r-AML. A similar analysis of CFU-A colonies revealed chromosomal aberrations in 25% of colonies derived from irradiated bone marrow (2% in controls). However, 66% of the aberrant colonies (2% in controls) exhibited ongoing genetic instability as defined by non-clonal chromosomal aberrations. Overall, 6% (121/1884) of the CFU-A cells derived from irradiated bone marrow were aberrant (0.05% in controls) of which 12% (15/121) were subclonal. No one CFU-A cell exhibited aberrations on more than one of the three chromosomes painted. CONCLUSIONS: The high levels of non-specific genetic damage observed in the r-AMLs is therefore attributed to the accumulation of genetic lesions in the target haemopoietic stem cell over a longer time-scale after exposure than assessed in the in vitro CFU-A clonogenic assay. This is consistent with the long latency of the multi-stage radiation leukaemogenic process, and a role for radiation-induced genetic instability is inferred.
Authors:
D MacDonald; E Boulton; D Pocock; D Goodhead; M Kadhim; M Plumb
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  77     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-29     Completed Date:  2001-12-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1023-31     Citation Subset:  IM; S    
Affiliation:
MRC Radiation and Genome Stability Unit, Chilton, Didcot, OXON, OX11 ORD, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromosome Aberrations*
Chromosome Disorders*
Hematopoietic Stem Cells / radiation effects*,  ultrastructure
In Situ Hybridization, Fluorescence
Leukemia, Myeloid, Acute / genetics*
Leukemia, Radiation-Induced / genetics*
Mice
Mice, Inbred CBA
X-Rays

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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