Suppression of diethylstilbestrol and N-nitrosobutylurea-induced mammary and pituitary tumorigenesis in rats by prolonged treatment with 2-bromoergocryptine.

Inbred male W/Fu rats were castrated at 40 days of age (24) and divided into five groups. Group I was given no further treatment. Groups II, IV, and V received pellet implants of 5.0 mg diethylstilbestrol (DES) concurrently with the castration. At 50 to 55 days of age, Groups II, IV, and V were given drinking water containing 5.0 mg N-nitrosobutylurea (NBU)/day for 30 days. This amount does not induce mammary tumors (MTs) in castrated male rats (24) or in female rats (31). At the termination of NBU treatment, Group V received further daily s.c. injections of 2-bromoergocryptine (CB-154; 0.4 mg/100 g body weight) four times/week throughout the experiment. None of the castrated rats or rats castrated and treated with NBU alone developed MT or pituitary tumors (PTs). Incidences of MT and PT in Groups III, IV, and V were three of nine (33%) and seven of nine (78%), 15 of 17 (88%) and 12 of 17 (17%), and three of 20 (15%) and four of 20 (20%), respectively. The treatment with DES alone resulted in the concurrent development of MT and PT in castrated male rats (Group III), and further NBU treatment markedly accelerated the development and growth of MT (Group IV). CB-154 treatment profoundly reduced the incidences of both MT and PT in castrated male rats given DES and NBU (Group V). This treatment also depressed the increase in the number of MT per rat with MT, the pituitary and epididymis weights, and the serum prolactin levels caused by DES treatment. These results indicate that prolonged treatment with CB-154 was effective in the suppression of the concurrent tumorigenesis of mammary and pituitary glands, and the elevation of circulating prolactin levels, by counteracting the continuous stimulatory action of DES. In addition, CB-154 was able to reverse DES-enhanced growth of the epididymis in castrated male rats, suggesting a direct action of prolactin.