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Biologic Characteristics and Chemotherapy of 7,12-Dimethylbenz[a]anthracene-induced Tumors in Rats¹

Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, and Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York, New York

The biologic characteristics and susceptibility to steroid therapy were determined for multiple mammary tumors induced in Sprague-Dawley rats by single intragastric doses of DMBA.³ Tumors were produced in 70–78% of 1016 rats within 120 days of administration of 15, 20, or 30 mg of DMBA. Mortality was 20% in rats given the highest dose. Only 52–63% of the rats had tumors usable for experimental chemotherapy. In 20 representative rats, 86 mammary tumors comprised 97.6% of all masses removed at autopsy, 92% of which were malignant. Growth behavior of tumors was unpredictable, a variable number growing, regressing, or remaining static in the same host. Bilateral ovariectomy on 70 rats produced tumor regression in 57%. These remained tumor free from 11 to less than 35 weeks. Steroids producing complete remission of all tumors in 40% or more of the treated rats were: 5-androstan-3, 17ß-diol dipropionate; 2-methyldihydrotestosterone; its propionate, testosterone propionate; 9-fluoro-11ß-hydroxy-17-methyltestosterone; and 6ß-methyldihydrotestosterone propionate. 1-Dehydrotestololactone was relatively inactive. Preliminary tests with nonsteroids yielded inconclusive results because of high toxicity.

¹ Supported by Contracts SA-ph-2445 and PH-43-65-619 from the Cancer Chemotherapy National Service Center, National Cancer Institute, USPHS.

³ The following abbreviations are used: DMBA, 7,12-dimethylbenz[a]anthracene; CR, complete remission; PR, partial remission; NR, nonresponder; AD, average diameter.

² Present address: Columbia University College of Pharmacy, New York, N. Y.

Received 8/ 9/65.