Abstract
The origin of chemically induced male accessory sex gland tumors was studied 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 incidence of prostate carcinomas in these rats with this treatment protocol. Additional animal groups included untreated controls, rats that received only an injection of 30 mg NMU/kg, and rats that were subjected to ablation of the seminal vesicle lobes prior to the treatment with NMU and testosterone. Three to 14 rats per group were sacrificed 4 to 10 months after NMU treatment and all remaining rats after 12 months. Twenty-four additional rats died or became moribund during the study. All rats were necropsied and the dorsolateral and ventral prostate and seminal vesicles with coagulating gland (anterior prostate) were examined histologically according to a standardized protocol. Lesions detected included atypical hyperplasia in all glands (resembling prostate intraepithelial neoplasia of human beings), adenomas in seminal vesicles only, and early carcinomas and adenocarcinomas in seminal vesicles and coagulating gland. Early carcinomas of the seminal vesicle, microscopically small and with invasion of the lamina propria and/or tunica muscularis, were detected as rapidly as 4 months after treatment. The vast majority (>95%) of the grossly visible nodules/masses originated from the seminal vesicles. Testosterone treatment enhanced occurrence and increased the incidence of all lesions, particularly of seminal vesicle 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 the parenchyma of the seminal vesicle/prostate complex after ablation. Thus, NMU-induced and testosterone-promoted male sex gland tumors of the Lobund-Wistar rat arise almost exclusively in the seminal vesicles and coagulating gland (anterior prostate), are highly invasive in seminal vesicles before attaining a grossly visible size, and progress rapidly within 4 months, spreading to adjacent tissues and other organs.