Skip Navigation


Carcinogenesis Advance Access originally published online on June 18, 2009
Carcinogenesis 2009 30(10):1776-1780; doi:10.1093/carcin/bgp146
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
30/10/1776    most recent
bgp146v1
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 Yan, B.
Right arrow Articles by Li, C.-Y.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yan, B.
Right arrow Articles by Li, C.-Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Increased skin carcinogenesis in caspase-activated DNase knockout mice

Bin Yan1,2,{dagger}, Huili Wang3,{dagger}, Donghua Xie3, Nobuko Wakamatsu4, Mitchell S. Anscher1, Mark W. Dewhirst2, Ron E.J. Mitchel5, Benny J. Chen3 and Chuan-Yuan Li2,6,*

1 Department of Radiation Oncology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA
2 Department of Radiation Oncology
3 Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
4 Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
5 Radiation Biology and Health Physics Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario K0J 1J0, Canada
6 Department of Radiation Oncology, University of Colorado Health Sciences Center, PO Box 6511, Mail Stop 8123, Aurora, CO 80045, USA

* To whom correspondence should be addressed. Tel: +1 303 724 1542; Fax: +1 303 724 1554; Email: chuan.li{at}uchsc.edu

Caspase-activated DNase (CAD), also called DNA fragmentation factor (DFF), is the enzyme responsible for DNA fragmentation during apoptosis, a hallmark of programmed cell death. CAD/DFF has been shown to suppress radiation-induced carcinogenesis by preventing genomic instability in cells. In this study, we have investigated the role of CAD in chemical carcinogenesis using CAD-null mice and two-stage model of skin carcinogenesis. After topical treatment of mouse skin with dimethylbenz[a]anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoting agent, there was a 4-fold increase in the number of papillomas per mouse and 50.8% increase in the incidence of papilloma formation in the CAD knockout mice compared with wild-type littermates. The papillomas in CAD-null mice grew faster and reached larger sizes. These data indicate that loss of CAD function enhances tumorigenesis induced by a chemical carcinogen in the DMBA/TPA two-stage model of skin carcinogenesis in mice.

Abbreviations: CAD, caspase-activated DNase; DFF, DNA fragmentation factor; DMBA, dimethylbenz[a]anthracene; ICAD, inhibitor of caspase-activated DNase; TPA, 12-O-tetradecanoylphorbol-13-acetate

{dagger} These authors contributed equally to this work.

Received January 31, 2008; revised September 9, 2008; accepted June 10, 2009.


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.