In Vivo Testing of Chemopreventive Agents using the Dog Model of Spontaneous Prostate Carcinogenesis
Abstract
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. From April 1, 2003 to March 31, 2004, we have further defined the anticancer effects of the trace mineral selenium on the aging prostate. Our work has generated the first evidence of a nonlinear, 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. In our Phase H proposal, we are focusing on interactions between selenium and the antiandrogen, finasteride. To accomplish this, we will conduct a 6 month intervention trial using elderly beagle dogs. At the time of this report, 57 dogs have undergone prostatic biopsy, randomized treatment assignment (no treatment, selenium alone, finasteride alone, or selenium plus finasteride), and necropsy after a 6 month intervention period. Interventions were well tolerated by all dogs. Biomarker analysis on tissues and body fluids collected pre- treatment, during the experimental period, and at time of euthanasia are currently in progress. Our experience indicates the dog model provides a useful model system to study the effects of cancer preventive agents on prostate cells in an appropriate context - in vivo within an aging prostate.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA428444
Entities
People
- David J. Waters
Organizations
- Purdue Research Foundation