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.