INDUCTION AT HIGH-INCIDENCE OF DUCTAL PROSTATE ADENOCARCINOMAS IN NBL/CR AND SPRAGUE-DAWLEY HSD-SD RATS TREATED WITH A COMBINATION OF TESTOSTERONE AND ESTRADIOL-17-BETA OR DIETHYLSTILBESTROL
INDUCTION AT HIGH-INCIDENCE OF DUCTAL PROSTATE ADENOCARCINOMAS IN NBL/CR AND SPRAGUE-DAWLEY HSD-SD RATS TREATED WITH A COMBINATION OF TESTOSTERONE AND ESTRADIOL-17-BETA OR DIETHYLSTILBESTROL
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DOI：
10.1093/carcin/16.6.1311
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发表时间：
1995-06-01
期刊：
影响因子：
4.7
通讯作者：
HORTON, L
中科院分区：
文献类型：
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作者：
BOSLAND, MC;FORD, H;HORTON, L
本研究确定了NBL和Sprague-Dawley大鼠接受雌二醇-17 β或己烯雌酚（DES）加睾酮长期治疗后前列腺腺癌的发生率，并确定了这些肿瘤的起源。NBL和Sprague-Dawley大鼠用两个硅橡胶管植入物（i.d. 1.6 mm，外径。3.2一个植入物含有2cm长的睾酮填充物，一个植入物含有1cm长的雌二醇-17 β或DES填充物。对照动物接受空植入物。在开始给药后91周（NBL）或75周（Sprague-Dawley）时，在濒死时杀死给药动物，并在开始给药后75周（Sprague-Dawley）杀死对照动物，并对附性腺进行采样，用于多个步骤切片的组织病理学检查。分别用雌二醇-17 β或DES加睾酮治疗44周和59周（组平均值）后，100%的NBL大鼠发生前列腺癌。Sprague-Dawley大鼠的腺癌发生率较低。腺癌是小的，显微镜下，浸润性肿瘤，它们在空间上密切相关的尿道周围导管的背侧，侧和/或前（=前列腺）前列腺，但从来没有与导管的腹叶和精囊。1例腺癌的来源不明。导管腺泡发育不良病变发生在外周的背侧和侧前列腺的所有前列腺素治疗的NBL和许多Sprague-Dawley大鼠，但似乎没有引起癌症。虽然有些腺癌与前列腺外周背外侧的异型增生导管相邻，但这些肿瘤的主要肿块位于尿道周围区域。此外，大多数腺癌仅与尿道周围导管相连，其中激素治疗36周或更长时间后发生不典型增生。因此，尿道周围前列腺导管的非典型增生，而不是周围导管腺泡发育不良，似乎是诱发癌的可能前兆。替吉奥加DES，而不是雌二醇-17 β，诱导所有NBL和许多Sprague-Dawley大鼠的腹侧前列腺泡明显发育不良样病变。在46%的NBL大鼠中，这些病变进展为原位癌（或腺瘤）。
This study determined the incidence of prostate adenocarcinoma following long-term treatment of NBL and Sprague-Dawley rats with estradiol-17 beta or diethylstilbestrol (DES) plus testosterone and it defined the origin of these tumors. NBL and Sprague-Dawley rats were treated with two Silastic tubing implants (i.d. 1.6 mm, o.d. 3.2 mm) containing a 2 cm long filling of testosterone and one implant containing a 1 cm long filling of estradiol-17 beta or DES. Control animals received empty implants. Treated animals were killed when moribund and controls were killed at 91 (NBL) or 75 (Sprague-Dawley) weeks after initiation of treatment and accessory sex glands were sampled for histopathological examination of multiple step sections. Prostatic adenocarcinoma occurred in 100% of NBL rats after treatment with estradiol-17 beta or DES plus testosterone for 44 and 59 weeks (group means) respectively. Adenocarcinoma incidences were lower in Sprague-Dawley rats. The adenocarcinomas were small, microscopic, invasive tumors and they were spatially closely associated with the periurethral ducts of the dorsal, lateral and/or anterior (= coagulating gland) prostate, but never with the ducts of the ventral lobe and seminal vesicles. One adenocarcinoma was of uncertain origin. Duct-acinar dysplastic lesions occurred in the periphery of the dorsal and lateral prostate of all hormone-treated NBL and many Sprague-Dawley rats, but did not appear to give rise to carcinoma. Although some adenocarcinomas were contiguous with dysplastic ducts of the peripheral dorsolateral prostate, the main mass of these neoplasms was located in the periurethral area. Also, most adenocarcinomas were only connected with the periurethral ducts, in which atypical hyperplasia occurred following hormone treatment for 36 weeks or longer. Thus atypical hyperplasia of the periurethral prostate ducts, but not peripheral duct-acinar dysplasia, appeared to be the likely precursor of the induced carcinomas. Testosterone plus DES, but not estradiol-17 beta, induced marked dysplasia-like lesions in the acini of the ventral prostate of all NBL and many Sprague-Dawley rats. These lesions had progressed to carcinoma in situ (or adenoma) in 46% of NBL rats.