Skip Navigation



Carcinogenesis Advance Access published online on August 10, 2005
Carcinogenesis, doi:10.1093/carcin/bgi207
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
27/2/311    most recent
bgi207v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Darakhshan, F.
Right arrow Articles by Bouffler, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Darakhshan, F.
Right arrow Articles by Bouffler, S. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received December 24, 2004
Revised August 1, 2005
Accepted August 2, 2005

CARCINOGENESIS

Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay

F. Darakhshan 1, C. Badie 2, J. Moody 2, M. Coster 2, R. Finnon 2, P. Finnon 2, A. A. Edwards 2, M. Szluinska 2, C. J. Skidmore 1, K. Yoshida 3, R. Ullrich 4, R. Cox 2, and S. D. Bouffler 2*

1 School of Animal and Microbial Sciences, University of Reading, Whiteknights, PO Box 228, Reading, Berkshire, RG6 6AJ
2 Radiation Effects Department, Health Protection Agency, Radiation Protection Division, Chilton, Didcot, Oxfordshire, OX11 0RQ, UK
3 NIRS, Inage-Ku, Chiba-shi 263, Japan
4 Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA

* To whom correspondence should be addressed.
S. D. Bouffler, E-mail: simon.bouffler{at}hpa-rp.org.uk


  Abstract

The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation AML risk modifier loci by association with microsatellite markers. A region on chromosome 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr 18 is identified. Rbbp8 is shown to be upregulated in response to x-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilising surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

Keywords: Radiation; acute myeloid leukaemia; mouse; chromosome 2; genetic mapping.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.