In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis
Final rept. 1 Sep 1998-28 Feb 2005
PURDUE RESEARCH FOUNDATION LAFAYETTE IN
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The goal of this research was to demonstrate the feasibility of the dog model of spontaneous prostate carcinogenesis as a valuable model system to evaluate chemopreventive agents. Our work has led to significant progress in elucidating the complex relationship between the essential trace mineral selenium and DNA damage, apoptosis, and androgens in the prostate. Our work has generated the first evidence of a non-linear, U-shaped dose response relationship between selenium status and DNA damage within the prostate. Importantly, the dose response curve from elderly beagle dogs accurately predicts the relationship between selenium status and prostate cancer risk in men. Moreover, we have demonstrated for the first time that supranutritional selenium intake is associated with increased apoptosis of prostatic epithelial cells in vivo. Our experimental paradigm has also yielded the first inforrnation on the influence of dietary selenium intake on intraprostatic levels of androgens. Interestingly, in the dog model, six months treatment with the 5-alpha reductase inhibitor finasteride with or without selenium induces prostatic atrophy without significantly reducing the extent of pro static DNA damage. Our experience indicates the dog model provides a useflil model system to study the effects of cancer preventive agents on prostate cells in an appropriate context - in vivo within an aging prostate.
- Medicine and Medical Research