Lycopene is a promising chemopreventive agent for prostate cancer (CAP). However, the actual effects of this dietary antioxidant on prostatic tissue are poorly understood. We propose to conduct a placebo-controlled randomized trial to investigate the effects of lycopene supplements (30 mg/day for six months) on molecular and cell morphology markers in core needle biopsy samples from men with documented HGPIN. Participants will be recruited from the Urology services at Northwestern Memorial Hospital and the Lakeside Veterans Administration Hospital. We propose the following specific aims: (1) Molecular markers in tissue. We will use conventional immunohistochemistry and computer based image analysis to test the hypothesis that the lycopene supplements alter the expression of proteins marking the status of proliferation, differentiation, cell regulation and apoptosis in high-risk tissue. (2) Nuclear morphometry. We will use a computerized image analysis system designed for the chemoprevention setting to test the hypothesis that the antioxidants cause a favorable change in a nuclear morphometry index based on nuclear size, shape and chromatin texture. (3) Serum androgen levels. We hypothesize, based on post hoc results of a phase III antioxidant trial, that the intervention will reduce levels of testosterone and alpha androstanediol glucuronide. (4) Growth factors in prostatic fluid (EGF). In previous work, we developed assays for EGF and TGF-beta 1 in EPF. We hypothesize that treatment reduces EGF and increases TGF-beta 1 in these prostatic secretions. (5) DNA oxidation markers in blood. We hypothesize that treatment decreases the oxidized bases HMdU and 8-OHdG in lymphocytes, and HMdU antibodies in serum detected by a novel ELISA method. Results of the proposed research will be useful for clarifying the mechanisms of action of lycopene in the prostate, for designing phase III trials, and, more generally, for determining the chemopreventive potential of this relatively non-toxic dietary compound.
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