Tamano S, Rehm S, Waalkes M P, Ward J M
Veterinary and Tumor Pathology Section, Office of Laboratory Animal Science, National Cancer Institute, Frederick, MD, USA.
Vet Pathol. 1996 Sep;33(5):557-67. doi: 10.1177/030098589603300511.
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.
在洛本德 - 威斯塔大鼠中研究了化学诱导的雄性附属性腺肿瘤的起源。3个月大的大鼠通过静脉单次注射30毫克N - 亚硝基甲基脲（NMU）/千克体重进行处理，并皮下植入填充有40毫克丙酸睾酮的硅橡胶植入物。先前的报告描述了采用这种治疗方案的这些大鼠中前列腺癌的高发病率。其他动物组包括未处理的对照组、仅接受30毫克NMU/千克注射的大鼠，以及在接受NMU和睾酮治疗之前进行精囊叶切除的大鼠。在NMU治疗后4至10个月，每组处死3至14只大鼠，12个月后处死所有剩余大鼠。在研究期间另有24只大鼠死亡或濒死。对所有大鼠进行尸检，并根据标准化方案对背外侧和腹侧前列腺以及带有凝固腺（前列腺前部）的精囊进行组织学检查。检测到的病变包括所有腺体的非典型增生（类似于人类前列腺上皮内瘤变）、仅精囊中的腺瘤，以及精囊和凝固腺中的早期癌和腺癌。精囊的早期癌在显微镜下较小，侵犯固有层和/或肌层，在治疗后4个月时就被快速检测到。绝大多数（>95%）肉眼可见的结节/肿块起源于精囊。睾酮治疗增加了所有病变的发生率，特别是精囊腺癌的发生率，从30%（7/23）增加到64%（21/33）。在21%（7/33）的大鼠中发现了凝固腺肿瘤。精囊叶切除将精囊腺癌的发生率降低到11%（3/29），并且这些肿瘤起源于切除后精囊/前列腺复合体实质内残留的组织。因此，洛本德 - 威斯塔大鼠中NMU诱导和睾酮促进的雄性性腺肿瘤几乎完全发生在精囊和凝固腺（前列腺前部），在达到肉眼可见大小之前在精囊中具有高度侵袭性，并在4个月内迅速进展，扩散到相邻组织和其他器官。
