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Characterization of Adenocarcinomas of the Dorsolateral Prostate Induced in Wistar Rats by N-Methyl-N-nitrosourea, 7,12-Dimethylbenz(a)anthracene, and 3,2'-Dimethyl-4-aminobiphenyl, following Sequential Treatment with Cyproterone Acetate and Testosterone Propionate¹

Department of Biological Toxicology, TNO-CIVO Toxicology and Nutrition Institute, P. O. Box 360, 3700 AJ Zeist, The Netherlands

Carcinomas of the rat prostate induced by a single injection of N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl, after sequential treatment with cyproterone acetate and testosterone propionate, were evaluated as potential animal models for prostatic cancer. All ten carcinomas examined were located in the dorsolateral prostate region and did not involve the distal parts of the seminal vesicles and coagulating glands. The incidence of urinary obstruction leading to the animals' death was 6 of 10 rats, and metastases in the lung, abdominal lymph nodes, and/or liver also occurred in 6 of 10 rats. The tumors were invasive adenocarcinomas, showing frequent perineural invasion and a variable degree of differentiation. There were ultrastructural similarities with human prostatic carcinomas, such as intracellular lumina. Plasma acid phosphatase was increased. Enzyme histochemical analysis revealed similarities with the Dunning R3327H and -HI prostatic carcinomas but was not helpful in determining the site of origin of the tumors. The gross and microscopic appearance of the tumors and the observation of preneoplastic lesions exclusively located in the dorsolateral prostate suggest this lobe as site of origin of the carcinomas. Preneoplastic lesions (n = 9) included atypical hyperplasias (n = 5) and lesions with all histological characteristics of carcinoma except for local invasion and metastases, which were classified as carcinoma in situ (n = 4). Although androgen sensitivity could not be assessed, the observed characteristics of the tumors [their long latency time (46–80 weeks), the presence of preneoplastic lesions, and the short duration of the treatment, leaving the animals intact] all indicate that the present approach is a valid animal model for the study of prostatic carcinogenesis.

¹ Supported in part by grants CIVO 80-3 and CIVO 84-3 from the Netherlands Cancer Foundation, Koningin Wilhelmina Fonds.

² Present address: Institute of Environmental Medicine, New York University Medical Center, 550 First Avenue, New York, NY 10016. To whom requests for reprints should be addressed. This work was submitted as part of a dissertation to the State University of Utrecht, The Netherlands, in partial fulfillment of the requirements for the Doctorate Degree.

Received 2/16/89. Revised 6/ 9/89. Revised 9/25/89. Accepted 10/26/89.

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