The effect of pregnant mares serum gonadotrophin on the response of DMBA induced rat mammary tumours to tamoxifen or oestrogen.
Ovariectomized and intact rats bearing mammary tumours, induced with 7,12-dimethylbenz(a)anthracene, were treated with diethylstilboestrol (DES), tamoxifen and pregnant mares serum gonadotrophin (PMSG) alone or in various combinations. In ovariectomized animals, PMSG (100 iu daily) alone, or with DES (50 micrograms) or tamoxifen (50 micrograms), slowed tumour regression. Mean tumour volume after 5 weeks was larger than control (P less than 0.05) in animals treated with PMSG + DES but not with PMSG or PMSG + tamoxifen. In intact animals, PMSG (200 iu bd, but not 2 or 20 iu bd) slowed tumour growth (P less than 0.05) and PMSG (2 or 200 iu bd) reversed the tumour inhibiting effect of tamoxifen (200 micrograms). PMSG (2 iu bd), in contrast to 20 and 200 iu doses, showed no evidence of oestrogen stimulation. It is suggested that the reversal of the tumour inhibiting effect of tamoxifen by this low dose of PMSG may be of relevance to failure of tamoxifen treatment and to 'tamoxifen flare'.
Clark
E R
ER
Department of Pharmacology, University of Leeds, U.K.
Robinson
S P
SP
Whitaker
E M
EM
Zoltowski
J A
JA
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004054:Diethylstilbestrol / Q000627:therapeutic use*; D004347:Drug Interactions; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000627:therapeutic use*
D006064:Gonadotropins, Equine; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D004054:Diethylstilbestrol