Antioxidant Prophylaxis in the Prevention of Prostatic Epithelial Neoplasia
Final rept. 1 Feb 2004-31 Jan 2007
TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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Clinically significant prostate cancer usually occurs in men who are 65 and older although precursor lesions are known to exist many years prior to cancer diagnosis. Histopathological changes referred to as Prostatic lntraepithelial Neoplasia PIN are considered to be the most likely precursor of prostate cancer. The mechanisms involved in progression of indolent to active disease remains elusive although a role for age-related increase in oxidative stress has been proposed. There are a variety of reactive oxygen species ROS that ultimately cause oxidative stress and any particular oxidant has not been identified as being primarily involved. We rationalized that a combination of antioxidants may be necessary to neutralize the different classes of ROS to prevent the progression of latent precursor foci to active cancer. Therefore we devised a combination of antioxidants with varied antioxidant properties to determine whether such supplementation could prevent the progression of PIN in Noble rats that are stimulated to develop PIN with hormones. Results from this study show for the first time that dietary intervention with a combination of antioxidants caused a highly significant decrease p 0.0004 in high grade PIN formation compared to animals on control diet possibly through modulation of proliferationapoptosis induction. These data provide evidence regarding the involvement of oxidants in the progression of precursor lesions and the need to evaluate combinations of antioxidants as prostate cancer preventive agents.
- Medicine and Medical Research