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.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002369:Castration; D002455:Cell Division / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006589:Hexestrol / Q000031:analogs & derivatives / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D013629:Tamoxifen; D006589:Hexestrol; D015127:9,10-Dimethyl-1,2-benzanthracene; C033293:NSC 297170; D004054:Diethylstilbestrol; C039150:1,1,2,2-tetramethyl-1,2-bis(4'-hydroxyphenyl)ethane