Trial to induce prostatic cancer in ACI/Seg rats treated with a combination of 3,2'-dimethyl-4-aminobiphenyl and ethinyl estradiol.
In an attempt to induce prostatic adenocarcinoma at higher incidence in a shorter period, we administered diet containing 0.75 ppm of ethinyl estradiol (EE) for three weeks to ACI/Seg rats, which are predisposed to develop a high incidence of microscopic adenocarcinoma of the prostate at higher age. Then, feeding was changed to basal diet and a single subcutaneous injection of 50 mg/kg body weight of 3,2'-dimethyl-4-aminobiphenyl (DMAB) was given two days after the change. We repeated this schedule 10 times. The rats were killed in week 60 of the experiment and subjected to routine autopsy. The average body weight of rats in group 1 given EE and DMAB was lower than that of control rats in group 2. The incidence of adenocarcinoma was not significantly different in the two groups, i.e., 6/74 (8.1%) in group 1 and 2/54 (3.7%) in group 2. The lesions were all microscopic. The incidence of atypical hyperplasia was significantly higher in group 1 at 17 of 74 rats (23.0%) whereas in group 2, it was only 2 of 54 rats (3.7%). Simple hyperplasia was also observed in 25 of 74 rats (33.8%) in group 1, which was significantly higher than that in group 2, where six of 54 rats (11.1%) had this lesion. The reduced growth of animals due to treatments with EE and DMAB probably suppressed the development of prostate cancer in this experiment. Further studies are needed to develop an appropriate model to induce prostate carcinoma at higher incidence in a shorter period.
Takai
K
K
Department of Urology, Faculty of Medicine, University of Tokyo.
Kakizoe
T
T
Tanaka
Y
Y
Tobisu
K
K
Aso
Y
Y
D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000139:chemically induced / Q000473:pathology; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; C001042:2',3-dimethyl-4-aminobiphenyl; D004997:Ethinyl Estradiol