Role of Estrogen Metabolism in the Initiation of Prostate Cancer: Biomarkers of Susceptibility and Early Detection
Annual rept. 1 May 2002-30 Apr 2003
NEBRASKA UNIV MEDICAL CENTER OMAHA
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Treatment of Noble rats with testosterone plus estradiol E2 induces prostate carcinomas. We think that estrogens initiate prostate cancer by reaction of catechol estrogen-3,4-quinone CE-3,4-Q metabolites with DNA. Formation of depurinating adducts by CE-3,4-Q, which generate apurinic sites in DNA, would be the critical event leading to mutations that initiate prostate cancer. After treatment of rats with CE or CE-3,4-Q, CE metabolites and CE-glutathione GSH conjugates were lower in regions where tumors develop and methoxyCE were higher in regions where tumors do not develop. To study the role of CE-Q in initiation of prostate cancer, we are 1 treating rats with E2 and currently analyzing the CE metabolites, CE-GSH conjugates and depurinating CE-DNA adducts in the regions of the prostate by HPLC with electrochemical and mass spectrometric detection 2 studying in the prostate conversion of testosterone into E2 and its metabolism and 3 currently determining the expression at the mRNA level of four selected enzymes involved in estrogen activation and deactivation in the prostate of rats treated with testosterone. These studies will provide information critical to understanding the molecular etiology of prostate cancer, identify biomarkers for early detection of susceptibility and lead to development of strategies for prostate cancer prevention.
- Medicine and Medical Research