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, 2002 to March 31, 2003, 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 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. In our Phase II proposal, we are focusing on interactions between selenium and the antiandrogen, finasteride. To accomplish this, we will conduct a 6 month intervention trial using 60 dogs. At the time of this report, 35 dogs have undergone prostatic biopsy and have been randomly assigned to receive no treatment, selenium alone, finasteride alone, or selenium plus finasteride. Interventions were well tolerated by all dogs. Additional dogs to complete this task will be studied during the project's approved 12 month extension period. Results of biomarker analysis on tissues and body fluids collected pre-treatment, during the experimental period, and at time of euthanasia are pending. Our experience indicates the dog model provides a useful 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
- Mar 01, 2003
- Accession Number
- ADA418684
Entities
People
- David J. Waters
Organizations
- Purdue Research Foundation