271 EXCESS DIETARY FOLATE INTAKE PROMOTES PROSTATE CARCINOGENESIS AND PROGRESSION IN AN IN VIVO MODEL OF TUMORIGENESIS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011271 EXCESS DIETARY FOLATE INTAKE PROMOTES PROSTATE CARCINOGENESIS AND PROGRESSION IN AN IN VIVO MODEL OF TUMORIGENESIS Jeffrey Tomaszewski, Jessica Cummings, Anil Parwani, Rajiv Dhir, Dean Bacich, and Denise O'Keefe Jeffrey TomaszewskiJeffrey Tomaszewski Pittsburgh, PA More articles by this author , Jessica CummingsJessica Cummings Pittsburgh, PA More articles by this author , Anil ParwaniAnil Parwani Pittsburgh, PA More articles by this author , Rajiv DhirRajiv Dhir Pittsburgh, PA More articles by this author , Dean BacichDean Bacich Pittsburgh, PA More articles by this author , and Denise O'KeefeDenise O'Keefe Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.363AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent studies demonstrate that folic acid supplementation is associated with an increased incidence of prostate cancer. We previously reported a positive correlation between serum and prostate tumor folate, and increased cancer cell proliferation in patients with higher serum folate concentrations. Our goal for this study was to determine the effect of dietary folate manipulation on prostate carcinogenesis and progression in an in vivo model. METHODS Prostate tumor and adjacent normal tissues from patients with prostate cancer were analyzed using the subrenal prostatic recapitulation model to determine the effect of dietary folate on tumor characteristics. Mice were randomly assigned to receive amino-acid defined diets which contained 0, 2 or 20mg/kg folic acid. Tissue recombinants (n=64) were serially grafted and harvested after 8, 16, and 24 weeks under the renal capsule. Histological and morphological features were assessed based upon 20 fields per recombinant, with the worst histological phenotype assigned to that recombinant. RESULTS Mice achieved serum folate levels that were consistent with the levels seen in human patients [i.e. approximately 2x adequate (24nM), 5x adequate (60nM) and 10 times adequate levels (120nM) for the 0, 2 and 20mg/kg folate diets, respectively]. Among normal prostate tissue recombinants, exposure to serum folate in the range of 5–10 fold adequate levels increased the incidence of PIN and adenocarcinoma when compared to recombinants grown in mice with serum folates 2-fold adequate levels (31.3% vs. 7%, respectively; p<0.05). An increased incidence of PIN and adenocarcinoma was also observed among prostate tumor recombinants in mice with 5–10 fold excess circulating folate when compared to the mice with 2-fold adequate levels (97.6% vs. 75.3%, respectively; p<0.05). CONCLUSIONS Modulation of dietary folate in an in vivo human prostate tissue recombinant model of tumorigenesis resulted in exposure to 5–10 fold excess levels of circulating folate, and promoted prostate carcinogenesis. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e109 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeffrey Tomaszewski Pittsburgh, PA More articles by this author Jessica Cummings Pittsburgh, PA More articles by this author Anil Parwani Pittsburgh, PA More articles by this author Rajiv Dhir Pittsburgh, PA More articles by this author Dean Bacich Pittsburgh, PA More articles by this author Denise O'Keefe Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...