SYNERGISTIC EFFECT OF CHRONIC PROLACTIN SUPPRESSION AND RETINOID TREATMENT IN THE PROPHYLAXIS OF N-METHYL-N-NITROSOUREA-INDUCED MAMMARY TUMORIGENESIS IN FEMALE SPRAGUE-DAWLEY RATS

Abstract

Sprague-Dawley rats (240) were treated i.v. with 2.5 or 1.25 mg of N-methyl-N-nitrosourea (MNU) per 100 g body weight at 50 and 57 days of age. At 60 days of age, rats given either dose were divided into 4 groups (30 rats/group) and treated as follows: Group 1, controls; Group 2, 0.4 mg 2-bromo-.alpha.-ergocryptine (CB-154) per 100 g body weight injected s.c. once daily; Group 3, retinyl acetate (328 mg/kg diet) fed daily; and Group 4, CB-154 and retinyl acetate treatments combined. Rats that received the 2.5 mg dose of MNU were treated for 129 days; those that received the 1.25 mg dose of MNU were treated for 175 days. The rats that were treated with the high dose of MNU were maintained without any treatment for an additional 13 wk, after which they were sacrificed. The rats that were treated with the low dose of the carcinogen were sacrificed immediately after treatment. All rats were palpated once weekly for palpable mammary tumors. The number of rats with mammary tumors and the total number of mammary tumors at cessation of treatments were, respectively, as follows: MNU (2.5 mg): MNU (2.5 mg): Group 1, 22 of 30 (73%), 82; Group 2, 11 of 30 (37%), 17; Group 3, 11 of 30 (37%), 19; Group 4, 2 of 30 (7%), 2. MNU (1.25 mg): Group 1, 8 of 30 (27%), 14; Group 2, 4 of 30 (13%), 5; Group 3, 3 of 30 (10%), 4; Group 4, 0 of 30, (0%), 0. Thus, chronic CB-154 treatment or retinyl acetate feeding markedly reduced the percentage of rats bearing mammary tumors and the total number of mammary tumors. The combined treatments were superior to either treatment alone, inasmuch as mammary tumorigenesis was nearly completely blocked in the rats of Group 4 that received the 2.5 mg dose of MNU and was totally blocked in the rats of Group 4 that received the 1.25 mg dose of MNU. Retinyl acetate feeding or CB-154-induced prolactin suppression appear to be equally effective treatments in the prophylaxis of MNU-induced mammary tumorigenesis in rats; the combined modality, however, appears to be far superior than either treatment alone.