Modification of the effect of a gonadoliberin analog on 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by hormone replacement.
A gonadoliberin analog, (D-leucyl6, desglycyl-NH2(10), prolyl ethylamide9) gonadoliberin, is known to suppress ovarian function and plasma prolactin levels. Its antitumor activity was evaluated against mammary tumors induced in Sprague-Dawley rats by dimethylbenz(a)anthracene. Observations were made when the analog, referred to as A-43818, was given alone and together with estrogen replacement or perphenazine, A-43818, 10 microgram s.c. twice a day for 6 weeks, was highly effective in producing tumor remissions. All of the 11 animals survived throughout the observation period, complete regressions occurred in 8 of 13 tumors, and 2 were classified as static. None of the 16 tumors  in 12 control rats regressed, and there were 4 deaths. When estradiol benzoate, 2 microgram s.c. each day, was administered with the A-43818, antitumor activity was suppressed; only 2 of 17 tumors regressed, 6 were static, and 5 of the 10 rats in this group died. Perphenazine, 1 mg i.m. daily, a dose known to cause hyperprolactinemia, also impaired the efficacy of A-43818. Three of 14 tumors regressed, 6 were static, and the rest continued to grow; 3 of the 12 rats died within 6 weeks of starting treatment.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006728:Hormones / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010053:Ovary / Q000187:drug effects; D010546:Perphenazine / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D051381:Rats
D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin; D010546:Perphenazine