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.