Do androgens contribute to the extent of genotoxic damage within the prostate?

B151

Previously, we have reported the utility of two non-invasive predictors of prostatic DNA damage: toenail selenium concentration and the sensitivity of peripheral blood lymphocytes to oxidative stress challenge. To further understand what factors contribute to the accumulation of DNA damage within the prostate, we tested the hypothesis that intraprostatic androgens are strongly associated with the extent of prostatic DNA damage. This hypothesis was tested in a population of 69 elderly male beagle dogs that had completed a 7-month randomized feeding trial to achieve the broad range of dietary selenium status observed in U.S. men. At the end of the treatment period, prostatic DNA damage was measured using alkaline Comet assay and dogs were subdivided into tertiles: low, medium, and high prostatic damage. Intraprostatic concentration of testosterone and dihydrotestosterone (DHT) as well as serum testosterone were determined for each dog using radioimmunoassay. Stepwise logistic regression was used to determine the relationship between intraprostatic testosterone and DHT concentration, and high prostatic damage. Dogs in the highest tertile of intraprostatic DHT were 4.6 times more likely to have high prostatic DNA damage than dogs in the lowest tertile of intraprostatic DHT (95% confidence interval = 0.96-21.9). When intraprostatic DHT was fit into a multivariate model including toenail selenium concentration and sensitivity of lymphocytes to oxidative stress challenge, it yielded the strongest predictive result (area under ROC curve = .82). In contrast, serum testosterone was not a significant predictor of high prostatic DNA damage. Moreover, serum testosterone was only weakly correlated with intraprostatic concentration of testosterone (r² = .036) and DHT (r² = .086). In conclusion, our data are consistent with the idea that intraprostatic androgens contribute to genotoxic damage within the prostate. However, serum testosterone does not provide a reliable non-invasive predictor of prostatic DNA damage.