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Variation in Tumor Yield in the Prostate and Other Target Organs of the Rat in Response to Varied Dosage and Duration of Administration of 3,2'-Dimethyl-4-aminobiphenyl¹

First Department of Pathology, Nagoya City University Medical School, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan

The effects of varying dosages of 3,2'-dimethyl-4-aminobiphenyl (DMAB) in combination with cyclic dietary administration of ethinyl estradiol (EE) on induction of prostate carcinoma were investigated in male F344 rats. Animals received repeated treatment with 0.75 ppm of EE for 3 wk with intervals of 2 wk on basal diet. The cycle was repeated 10, 5, and 3 times in Groups 1, 2, and 3, respectively, a single s.c. injection of DMAB being given 2 days after each change to basal diet at a dose of 50 mg/kg of body weight in Group 1, 100 mg/kg of body weight in Group 2, and 167 mg/kg of body weight in Group 3. With this dosing schedule, the total dose of DMAB (500 mg/kg of body weight) per rat was the same in each group. Subsequent to the last treatment with EE, all rats were given basal diet until the end of the experiment (Wk 60) when all surviving animals were sacrificed for histological examination. Carcinoma of the prostate was found in 58.6, 45.0, and 25.9% of rats surviving for 60 wk in Groups 1 to 3, respectively, the incidences of atypical hyperplasia being 86.2, 85.0, and 74.1%. However, tumors of the small and large intestines, preputial gland, and pancreas developed in a dosage-dependent manner, the largest incidences being found in the group given 167 mg of carcinogen 3 times.

Thus the present experiment confirmed that administration of DMAB combined with cyclic treatment with EE induces a high incidence of prostate carcinoma in rats and demonstrated that a low dosage of DMAB given over a long period is superior to a high dosage over a short period for specific induction of prostate lesions.

¹ This research was supported in part by grants-in-aid for cancer research from the Ministry of Education, Science, and Culture and from the Ministry of Health and Welfare of Japan and a grant-in-aid from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control, Japan.

² To whom requests for reprints should be addressed.

Received 1/19/88. Revised 4/18/88. Accepted 5/20/88.

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