The studies proposed in this application will further develop and validate a model of chemically-induced prostate cancer in the male rat, using 3,2'-dimethyl-4-aminobiphenyl (DMAB) or methylnitrosourea (MNU). We have already described DMAB-induced intraacinar, in situ prostatic adenocarcinomas in F344 rats, which reached an incidence of almost 30% by somewhat over one year. Preliminary studies have indicated that our proposed MNU model will result in approximately 30% grossly visible prostatic adenocarcinomas in less than one year. We will, therefore, determine the prostate-cancer-inducing potential of DMAB in the MNU model and further develop the MNU model. Eight-week-old male F344, ACI/segHap BR and Sprauge Dawley rats will be used. All are fed standard NIH-07 diet with 15% wheat bran added. The bran will decrease the incidence of DMAB-induced colon cancer, while not affecting prostatic cancer incidence. The rats are pretreated with the antiandrogen cyproterone acetate for 21 days and then for 3 days will be injected with testosterone. On day 25 they will receive one of two dosage levels of DMAB which will be continued, with testosterone, for 80 or 180 days. Another group will receive, I.V., MNU for 3 successive days. Termination is anticipated 12-15 months after the intial carcinogen injection. The prostate will be examined using close-step sections. Other organs will be examined for metastases. Until we discovered the occurrence of chemically-induced prostatic cancer in this Institute, there were no reliable, relatively rapid ways of inducing this type of important human cancer. When fully developed, this model will provide a means for evaluating preventative, diagnostic and therapeutic modalities against autochthonous prostate cancer.
NIH ExPorter
NIH ExPorter