Bosland M C, Prinsen M K
Department of Biological Toxicology, TNO-CIVO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Cancer Res. 1990 Feb 1;50(3):691-9.
Groups of 20-25 male Wistar rats (Cpb:WU), nine groups of 4-week-old rats, and nine groups of 8-week-old rats, were given cyproterone acetate (CA) s.c. or by gavage daily for 18 days at a dose of 50 mg/kg/day. Directly following CA treatment, the rats received 3 daily s.c. injections with testosterone propionate (TP) at a dose of 100 mg/kg/day. On the day after the last TP administration, a single dose of one of the following carcinogens was given to 3 groups: N-methyl-N-nitrosourea (MNU), 50 mg/kg i.v.; 7,12-dimethylbenz(a)anthracene, 30 mg/kg i.v.; 3,2'-dimethyl-4-aminobiphenyl, 250 mg/kg s.c. Three other groups received the same carcinogen treatments after 7 days of recovery from the CA administration. The last 3 groups received carcinogen without TP treatment, but immediately after CA pretreatment was stopped. A 25% incidence of invasively growing, metastasizing adenocarcinomas was found in the dorsolateral prostate region of 8-week-old rats that had received MNU after treatment with CA plus TP. In addition, this group had a 5% incidence of carcinoma in situ and a 5% incidence of atypical hyperplasia in the dorsolateral prostate. Lower incidences of adenocarcinoma of the dorsolateral prostate region and of carcinoma in situ and atypical hyperplasia of the dorsolateral prostate were found in other groups that were treated with MNU or 7,12-dimethylbenz(a)anthracene after pretreatment with CA, followed by TP or recovery, but never in rats that had been treated with CA only. In the groups treated with 3,2'-dimethyl-4-aminobiphenyl, which is slowly metabolized, these lesions were also found in groups that were pretreated with only CA. The carcinomas seemed to originate from the dorsolateral prostate and their average latency time was approximately 61 weeks. The 8-week-old rat given a MNU injection after sequential treatment with CA and TP may provide a relevant animal model for human prostatic cancer.
将20 - 25只雄性Wistar大鼠（Cpb:WU）分为若干组，其中包括9组4周龄大鼠和9组8周龄大鼠，每天皮下注射或灌胃给予醋酸环丙孕酮（CA），剂量为50 mg/kg/天，持续18天。CA治疗结束后，大鼠每天皮下注射3次丙酸睾酮（TP），剂量为100 mg/kg/天。在最后一次给予TP后的第二天，给3组大鼠单次注射下列致癌物之一：N - 甲基 - N - 亚硝基脲（MNU），静脉注射剂量为50 mg/kg；7,12 - 二甲基苯并(a)蒽，静脉注射剂量为30 mg/kg；3,2'-二甲基 - 4 - 氨基联苯，皮下注射剂量为250 mg/kg。另外3组在从CA给药恢复7天后接受相同的致癌物处理。最后3组未接受TP处理，但在CA预处理停止后立即接受致癌物处理。在8周龄大鼠中，经CA加TP处理后接受MNU的大鼠，其背外侧前列腺区域发现有25%的侵袭性生长、转移性腺癌发生率。此外，该组原位癌发生率为5%，背外侧前列腺非典型增生发生率为5%。在经CA预处理后再接受TP或恢复，然后用MNU或7,12 - 二甲基苯并(a)蒽处理的其他组中，背外侧前列腺区域腺癌以及背外侧前列腺原位癌和非典型增生的发生率较低，但仅接受CA处理的大鼠中从未发现这些病变。在用代谢缓慢的3,2'-二甲基 - 4 - 氨基联苯处理的组中，仅用CA预处理的组也发现了这些病变。这些癌似乎起源于背外侧前列腺，其平均潜伏期约为61周。经CA和TP序贯处理后接受MNU注射的8周龄大鼠可能为人类前列腺癌提供一个相关的动物模型。
