Skip Navigation



Carcinogenesis Advance Access published online on May 27, 2004
Carcinogenesis, doi:10.1093/carcin/bgh191
© 2004 by Oxford University Press
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
25/10/1821    most recent
bgh191v1
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 Young, L. C.
Right arrow Articles by Andrew, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Young, L. C.
Right arrow Articles by Andrew, S. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received November 25, 2003
Revised May 3, 2004
Accepted May 16, 2004

CANCER BIOLOGY

DNA mismatch repair proteins promote apoptosis and suppress tumorigenesis in response to UVB irradiation: an in vivo study

Leah C. Young 1, Kyle J. Thulien 1, Marcia R. Campbell 1, Victor A. Tron 2, Susan E. Andrew 3*

1 Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
2 Department of Experimental Oncology, University of Alberta, Edmonton, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
3 Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada; Department of Experimental Oncology, University of Alberta, Edmonton, Alberta, Canada

* To whom correspondence should be addressed. E-mail: susan.andrew{at}ualberta.ca.


  Abstract

DNA mismatch repair (MMR) proteins are integral to the maintenance of genomic stability and suppression of tumorigenesis due to their role in repair of post-replicative DNA errors. Recent data also support a role for MMR proteins in the cellular responses to exogenous DNA damage that does not involve removal of DNA adducts. We have previously demonstrated that both Msh2- and Msh6-null primary mouse embryonic fibroblasts are significantly less sensitive to UVB-induced cytotoxicity and apoptosis than wildtype control cells. In order to ascertain the physiological relevance of these data we have exposed MMR-deficient mice to acute and chronic UVB radiation. We found that MMR-deficiency was associated with reduced levels of apoptosis and increased residual UVB-induced DNA adducts in the epidermis 24 hours following acute UVB exposure. Moreover, Msh2-null mice developed UVB-induced skin tumors at a lower level of cumulative UVB exposure and with a greater severity of onset than wildtype mice. The Msh2-null skin tumors did not display microsatellite instability, suggesting that these tumors develop via a different tumorigenic pathway than tumors that develop spontaneously. Therefore, we propose that dysfunctional MMR promotes UVB induced tumorigenesis through reduced apoptotic elimination of damaged epidermal cells.

Key Words: DNA mismatch repair, apoptosis, UVB, skin cancer


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 MutagenesisHome page
P. Pitsikas, D. Lee, and A. J. Rainbow
Reduced host cell reactivation of oxidative DNA damage in human cells deficient in the mismatch repair gene hMSH2
Mutagenesis, May 1, 2007; 22(3): 235 - 243.
[Abstract] [Full Text] [PDF]


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.