Pour P M, Stepan K
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha 68105.
Cancer Res. 1987 Nov 1;47(21):5699-706.
The effect of exogenous testosterone on prostatic carcinogenicity of N-nitrosobis(2-oxopropyl)amine (BOP) in intact and castrated rats was examined in Wistar-derived MRC rats. Daily administration of BOP (either s.c. or i.g.) for 3 days, at a dose of 20 mg/kg b.w. at the heights of prostatic cell proliferation induced by testosterone, led to development of a large number of prostatic tumors, the incidence of which, however, was dependent on the duration of testosterone administration. Testosterone given for life following BOP administration induced prostatic cancer in over 60% of rats, regardless of whether BOP was given orally or s.c., or whether the rats were orchiectomized or not, whereas tumor incidence was significantly lower in rats treated with testosterone for only a short period of time. One (3%) orchiectomized rat, which received testosterone only during BOP treatment, and four (15%) of rats treated with testosterone only for life also developed carcinomas. Histologically, a large number of BOP + testosterone-induced prostatic tumors were adenocarcinomas of various histological patterns and arose primarily from the dorsal lobe, whereas the great majority of squamous cell carcinomas were found in the ventral lobe. Simultaneously induced tumors were papillomas and carcinomas of the urinary bladder and urethra. Testosterone appeared to enhance the incidence of urinary bladder tumors, but not of the urethral tumors, whereas orchiectomy inhibited urethral carcinogenesis, and, to much lesser extent, urinary bladder tumor development. Rats treated weekly for 20 weeks with BOP (10 mg/kg/week i.g.) did not develop any prostatic tumors and all rats died of rectal cancer. Of rats treated similarly with BOP and with testosterone pellets for life following the last injection of BOP, 17% of rats developed prostatic cancer, all of the squamous cell type. Simultaneous testosterone and BOP treatment for 20 weeks followed by testosterone pellets for life resulted in a 39% tumor incidence (three adenocarcinomas, one anaplastic carcinoma, and five squamous cell carcinomas). The overall results suggest that testosterone plays an important role in the initiation of prostatic carcinogenesis, whereas the promotional phase is governed by the interaction of testosterone with other factors.
在源自Wistar的MRC大鼠中，研究了外源性睾酮对完整和去势大鼠中N-亚硝基双（2-氧代丙基）胺（BOP）前列腺致癌性的影响。在睾酮诱导前列腺细胞增殖的高峰期，以20mg/kg体重的剂量每日给予BOP（皮下或灌胃）3天，导致大量前列腺肿瘤的发生，然而，其发生率取决于睾酮给药的持续时间。在给予BOP后终身给予睾酮，超过60%的大鼠发生前列腺癌，无论BOP是口服还是皮下给药，也无论大鼠是否接受去势手术，而仅在短时间内给予睾酮治疗的大鼠肿瘤发生率显著较低。一只（3%）仅在BOP治疗期间接受睾酮的去势大鼠和四只（15%）仅终身接受睾酮治疗的大鼠也发生了癌。组织学上，大量BOP + 睾酮诱导的前列腺肿瘤是各种组织学类型的腺癌，主要起源于背叶，而绝大多数鳞状细胞癌见于腹叶。同时诱导的肿瘤是膀胱和尿道的乳头状瘤和癌。睾酮似乎增加了膀胱肿瘤的发生率，但未增加尿道肿瘤的发生率，而去势抑制了尿道致癌作用，并且在较小程度上抑制了膀胱肿瘤的发生。每周用BOP（10mg/kg/周，灌胃）治疗20周的大鼠未发生任何前列腺肿瘤，所有大鼠均死于直肠癌。在最后一次注射BOP后，用BOP和睾酮丸终身类似治疗的大鼠中，17%的大鼠发生了前列腺癌，均为鳞状细胞类型。同时给予睾酮和BOP治疗20周，然后终身给予睾酮丸，肿瘤发生率为39%（3例腺癌、1例间变性癌和5例鳞状细胞癌）。总体结果表明，睾酮在前列腺癌发生的起始阶段起重要作用，而促进阶段则受睾酮与其他因素相互作用的支配。
