Tumor growth-stimulating and inhibiting effects of antiestrogens on the DMBA-induced mammary carcinoma of the ovariectomized, diethylstilbestrol-treated SD rat. A study on the mechanism of action of antiestrogens.

After ovariectomy DMBA tumor-bearing SD rats were treated with the estrogen DES, a combination of DES plus mammary tumor-inhibiting antiestrogen (tetramethylHES, 3,3'HES and tamoxifen respectively) or with tetramethylHES alone. Small doses of DES led to a stimulation of tumor growth showing a maximum effect at 1 microgram/kg/day, whereas higher doses inhibited tumor growth. In the combination experiment only tetramethylHES reduced, i.e. antagonized, the DES effect. Tamoxifen and 3,3'HES, however, led to an increase of the tumor growth-stimulating and inhibiting effects of DES. Only the dose of 10 mg/kg/day of tetramethylHES led to a slight stimulation of the tumor growth in ovariectomized DMBA tumor-bearing rats. These results indicate that 3,3'HES and tamoxifen possibly unfold their mammary tumor-inhibiting activity by means of their estrogenic potency, whereas tetramethylHES might act as an antiestrogen, though the latter compound does not lack estrogenic activity completely.