Role of ovarian hormones in mammary tumorigenesis by a continuous oral administration of N-nitrosobutylurea in Wistar-Furth rats.

Abstract

This evaluates the role of ovarian hormones in the genesis progression or regression of mammary tumors induced by the continuous oral administration of N-nitrosobutylurea (NBU) to Wistar-Furth strain rats. 84 rats 4 weeks old and of both sexes were used. The NBU was dissolved in ethanol then in the animals drinking water to a concentration of 5 mg per 15 ml. The drinking bottle was shielded from light to prevent deterioration of the NBU. Mammary tumors were successfully induced in young female rats by continuous oral administration of a daily dose of 2.5 or 5 mg NBU per rat with a latent period of 6-8 months 10 mg per day caused marked suppression in body growth estrous and an the induction rate of mammary tumors. Ovariectomy prior to NBU treatment abolished the mammary tumorigenic effect while orchidectomy did not elicit mammary tumors in male rats. Restoration of mammary tumor development was attained in castrated rats of both sexes either by supplemental treatment with biweekly injections of .4 mg of progesterone combined with .01 mg of estradiol benzoate or by ovarian isograft implanted under the kidney capsule. Male rat. responded more promptly with tumor development than females. However after cessation of hormone treatment 7 months after beginning NBU therapy a rapid increase in mammary tumors occurred in ovariectomized and hormone treated rats. Castrated male rats are considered to be a useful tool for testing mammary tumorigenicity of unknown agents if conditioned adequately by ovarian hormones. Their productivity of mammary tumors is excellent in terms of incidence multiplicity and growth rate of tumors.