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  • Title: Antitumoral and endocrine effects of (+)-vorozole in rats bearing dimethylbenzanthracene-induced mammary tumors.
    Author: De Coster R, Van Ginckel RF, Callens MJ, Goeminne NK, Janssens BL.
    Journal: Cancer Res; 1992 Mar 01; 52(5):1240-4. PubMed ID: 1737385.
    Abstract:
    The antitumoral activity of vorozole, a potent and specific nonsteroidal aromatase inhibitor, against 7,12-dimethylbenz(a)anthracene-induced estrogen-dependent mammary adenocarcinoma was evaluated in 257 Sprague-Dawley rats. Twice daily p.o. administration of 1 and 5 mg/kg of the racemate R 76713 for 42 days induced almost complete regression of tumors, inhibited the appearance of new tumors, and reduced multiplicity of the remaining tumors. Antitumoral effects observed after ovariectomy or treatment with 5 mg/kg twice a day were not significantly different. R 76713, the racemate, (+)-vorozole (both at 2.5 mg/kg twice a day), and ovariectomy all similarly reduced tumor growth at 42 days by 90% or more, lowered the number of existing tumors, and prevented the appearance of new tumors. The less active levo-enantiomer (-)-vorozole at the same dose did not alter tumor growth. Vorozole reduced serum estradiol to the levels measured in ovariectomized animals. Serum progesterone levels were lowered, but to a much lesser extent than after ovariectomy, while serum luteinizing hormone and follicle-stimulating hormone concentrations increased, but also much less than after ovariectomy. On the other hand, the androgen levels, which remained undetectable or decreased after ovariectomy, markedly rose after vorozole treatment. These endocrine changes, observed in intact female rats, were not detected in ovariectomized animals demonstrating the ovarian origin of the endocrine changes induced by vorozole.
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