Skip Navigation



Carcinogenesis Advance Access published online on April 7, 2005
Carcinogenesis, doi:10.1093/carcin/bgi077
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
26/7/1256    most recent
bgi077v1
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 Waters, D. J.
Right arrow Articles by Morris, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Waters, D. J.
Right arrow Articles by Morris, J. S.
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 November 18, 2004
Revised March 15, 2005
Accepted March 22, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model

David J. Waters 1*, Shuren Shen 1, Lawrence T. Glickman 2, Dawn M. Cooley 1, David G. Bostwick 3, Junqi Qian 3, Gerald F. Combs Jr4, and J. Steven Morris 5

1 Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN, 47907; Gerald P. Murphy Cancer Foundation, West Lafayette, IN 47906
2 Department of Veterinary Pathobiology, Purdue University, West Lafayette, IN, 47907
3 Bostwick Laboratories, Richmond, VA 23294
4 Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853
5 University of Missouri-Columbia Research Reactor Center, Columbia, MO, 65211

* To whom correspondence should be addressed.
David J. Waters, E-mail: dwaters{at}gpmcf.org


  Abstract

Daily supplementation with the essential trace mineral selenium significantly reduced prostate cancer risk in men in the Nutritional Prevention of Cancer Trial. However, the optimal intake of selenium for prostate cancer prevention is unknown. We hypothesized that selenium significantly regulates the extent of genotoxic damage within the aging prostate and that the relationship between dietary selenium intake and DNA damage is non-linear, i.e. more selenium is not necessarily better. To test this hypothesis, we conducted a randomized feeding trial in which 49 elderly beagle dogs (physiologically equivalent to 62-69 year old men) received nutritionally adequate or supranutritional levels of selenium for 7 months, in order to mimic the range of dietary selenium intake of men in the United States. Our results demonstrate an intriguing U-shaped dose-response relationship between selenium status (toenail selenium concentration) and the extent of DNA damage (alkaline Comet assay) within the prostate. Further, we demonstrate that the concentration of selenium that minimizes DNA damage in the aging dog prostate remarkably parallels the selenium concentration in men that minimizes prostate cancer risk. By studying elderly dogs, the only non-human animal model of spontaneous prostate cancer, we have established a new approach to bridge the gap between laboratory and human studies that can be used to select the appropriate dose of anticancer agents for large-scale human cancer prevention trials. From the U-shaped dose-response, it follows that not all men will necessarily benefit from increasing their selenium intake and that measurement of baseline nutrient status should be required for all individuals in prevention trials to avoid oversupplementation.

Keywords: chemoprevention; carcinogenesis; dietary supplements; Comet assay; animal model; dog.
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
 CarcinogenesisHome page
U. Gundimeda, J. E. Schiffman, S. N. Gottlieb, B. I. Roth, and R. Gopalakrishna
Negation of the cancer-preventive actions of selenium by over-expression of protein kinase C{varepsilon} and selenoprotein thioredoxin reductase
Carcinogenesis, September 1, 2009; 30(9): 1553 - 1561.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. M. Chan, W. K. Oh, W. Xie, M. M. Regan, M. J. Stampfer, I. B. King, M. Abe, and P. W. Kantoff
Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate- or High-Risk Prostate Cancer
J. Clin. Oncol., August 1, 2009; 27(22): 3577 - 3583.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
D. N. Syed, N. Khan, F. Afaq, and H. Mukhtar
Chemoprevention of Prostate Cancer through Dietary Agents: Progress and Promise
Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2193 - 2203.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
D. J. Waters, S. Shen, H. Xu, S. S. Kengeri, D. M. Cooley, E. C. Chiang, Y. Chen, D. Schlittler, C. Oteham, G. F. Combs Jr., et al.
Noninvasive Prediction of Prostatic DNA Damage by Oxidative Stress Challenge of Peripheral Blood Lymphocytes
Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1906 - 1910.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. L. Sabichi, J. J. Lee, R. J. Taylor, I. M. Thompson, B. J. Miles, C. M. Tangen, L. M. Minasian, L. L. Pisters, J. R. Caton, J. W. Basler, et al.
Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of l-selenomethionine: a Southwest Oncology Group Study.
Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 2178 - 2184.
[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.