Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17{beta} or diethylstilbestrol

This study determined the incidence of prostate adenocarcinomafollowing long-term treatment of NBL and Sprague-Dawley ratswith estradiol-17ß or diethylstilbestrol (DES) plustestosterone and it defined the origin of these tumors. NBLand Sprague-Dawley rats were treated with two Silastic tubingimplants (i.d. 1.6 mm, o.d. 3.2 mm) containing a 2 cm long fillingof testosterone and one implant containing a 1 cm long fillingof estradiol-17ß or DES. Control animals receivedempty implants. Treated animals were killed when moribund andcontrols were killed at 91 (NBL) or 75 (Sprague-Dawley) weeksafter initiation of treatment and accessory sex glands weresampled for histopathological examination of multiple step sections.Prostatic adenocarcinoma occurred in 100% of NBL rats aftertreatment with estradiol-17ß or DES plus testosteronefor 44 and 59 weeks (group means) respectively. Adenocarcinomaincidences were lower in Sprague-Dawley rats. The adenocarcinomaswere small, microscopic, invasive tumors and they were spatiallyclosely associated with the periurethral ducts of the dorsal,lateral and/or anterior (= coagulating gland) prostate, butnever with the ducts of the ventral lobe and seminal vesicles.One adenocarcinoma was of uncertain origin. Duct-acinar dysplasticlesions occurred in the periphery of the dorsal and lateralprostate of all hormone-treated NBL and many Sprague-Dawleyrats, but did not appear to give rise to carcinoma. Althoughsome adenocarcinomas were contiguous with dysplastic ducts ofthe peripheral dorsolateral prostate, the main mass of theseneoplasms was located in the periurethral area. Also, most adenocarcinomaswere only connected with the periurethral ducts, in which atypicalhyperplasia occurred following hormone treatment for 36 weeksor longer. Thus atypical hyperplasia of the periurethral prostateducts, but not peripheral duct-acinar dysplasia, appeared tobe the likely precursor of the induced carcinomas. Testosteroneplus DES, but not estradiol-17ß), induced marked dysplasia-likelesions in the acini of the ventral prostate of all NBL andmany Sprague-Dawley rats. These lesions had progressed to carcinomain situ (or adenoma) in 46% of NBL rats.