Authors: Waters, David J.¹; Shen, Shuren¹; Glickman, Lawrence T.²; Cooley, Dawn M.¹; Bostwick, David G.³; Qian, Junqi³; Combs, Gerald F.⁴; Morris, J. Steven⁵

Source: Carcinogenesis, Volume 26, Number 7, 1 July 2005 , pp. 1256-1262(7)

Publisher: Oxford University Press

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.

Document Type: Research article

DOI: http://dx.doi.org/10.1093/carcin/bgi077

Affiliations: 1: Department of Veterinary Clinical Sciences and 2: Department of Veterinary Pathobiology, Purdue University, West Lafayette, IN 47907, USA, 3: Bostwick Laboratories, Richmond, VA 23294, USA, 4: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA, 5: University of Missouri-Columbia Research Reactor Center, Columbia, MO 65211, USA and

Publication date: 2005-07-01

More about this publication?

• Carcinogenesis is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal will publish papers that warrant prompt publication in the areas of Cancer Biology, Molecular Epidemiology and Cancer Prevention, and Carcinogenesis.

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• By this author: Waters, David J. ;  Shen, Shuren ;  Glickman, Lawrence T. ;  Cooley, Dawn M. ;  Bostwick, David G. ;  Qian, Junqi ;  Combs, Gerald F. ;  Morris, J. Steven

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