HIGH-INCIDENCE AND HISTOGENESIS OF SEMINAL-VESICLE ADENOCARCINOMA ANDLOWER INCIDENCE OF PROSTATE CARCINOMAS IN THE LOBUND-WISTAR PROSTATE-CANCER RAT MODEL USING N-NITROSOMETHYLUREA AND TESTOSTERONE

The origin of chemically induced male accessory sex gland tumors was s tudied in Lobund-Wistar rats. Rats were treated at the age of 3 months with a single intravenous injection of 30 mg N-nitrosomethylurea (NMU )/kg body weight and given subcutaneous silastic implants filled with 40 mg testosterone propionate. Previous reports described a high incid ence of prostate carcinomas in these rats with this treatment protocol . Additional animal groups included untreated controls, rats that rece ived only an injection of 30 mg NMU/kg, and rats that were subjected t o ablation of the seminal vesicle lobes prior to the treatment with NM U and testosterone. Three to 14 rats per group were sacrificed 4 to 10 months after NMU treatment and all remaining rats after 12 months. Tw enty-four additional rats died or became moribund during the study. Al l rats were necropsied and the dorsolateral and ventral prostate and s eminal vesicles with coagulating gland (anterior prostate) were examin ed histologically according to a standardized protocol. Lesions detect ed included atypical hyperplasia in all glands (resembling prostate in traepithelial neoplasia of human beings), adenomas in seminal vesicles only, and early carcinomas and adenocarcinomas in seminal vesicles an d coagulating gland. Early carcinomas of the seminal vesicle, microsco pically small and with invasion of the lamina propria and/or tunica mu scularis, were detected as rapidly as 4 months after treatment. The va st majority (>95%) of the grossly visible nodules/masses originated fr om the seminal vesicles. Testosterone treatment enhanced occurrence an d increased the incidence of all lesions, particularly of seminal vesi cle adenocarcinomas, from 30% (7/23) to 64% (21/33). Coagulating gland tumors were found in 21% (7/33) of the rats. Ablation of the seminal vesicle lobes reduced the incidence of seminal vesicle adenocarcinomas to 11% (3/29), and these tumors arose from tissues remaining within t he parenchyma of the seminal vesicle/prostate complex after ablation. Thus, NMU-induced and testosterone-promoted male sex gland tumors of t he Lobund-Wistar rat arise almost exclusively in the seminal vesicles and coagulating gland (anterior prostate), are highly invasive in semi nal vesicles before attaining a grossly visible size, and progress rap idly within 4 months, spreading to adjacent tissues and other organs.