title: Aromatase inhibition by R 83 842, the dextro isomer of R 76 713, in JEG-3 choriocarcinoma grown in ovariectomized nude mice.
abstract: The effects of repeated (5 days) dosing with the non-steroidal aromatase inhibitor R 83 842 (the dextro isomer of R 76 713) on tumor aromatase and uterus weight in ovariectomized nude mice bearing JEG-3 tumors were examined. In animals bearing an androstenedione implant the presence of a JEG-3 tumor significantly increased uterus weight, proving that tumor aromatase indeed converted androgens to estrogens. Oral administration of R 76 713 (10 mg/kg) for 5 days reduced the increase in uterus weight by 84% in tumor bearing mice revealing true in vivo aromatase inhibition by R 76 713. Experiments performed in the absence of exogenously added androgens gave similar results. Uterus weights in tumor bearing mice were significantly higher than in control mice. Oral administration of R 83 842 (5 mg/kg) for 5 days reduced uterus weight in the tumor bearing animals. Ex vivo aromatase measurements performed in JEG-3 tumors from these animals showed an aromatase inhibition of 93.9% in treated mice as compared to untreated mice. Five days oral treatment with R 83 842 dose-dependently lowered both aromatase activity and uterus weight. Doses of 5 and 0.5 mg/kg inhibited tumor aromatase by 94.1 and 74.7%, respectively, and reduced uterus weight. After a dose of 0.05 mg/kg aromatase activity and uterus weight were similar to those in the control group.
authors.affiliation: Department of Endocrinology and Oncology, Janssen Research Foundation, Beerse, Belgium.
authors.forename: M D
authors.initials: MD
authors.lastname: Krekels
authors.forename: W
authors.initials: W
authors.lastname: Wouters
authors.forename: R
authors.initials: R
authors.lastname: Van Ginckel
authors.forename: B
authors.initials: B
authors.lastname: Janssens
authors.forename: M
authors.initials: M
authors.lastname: Callens
authors.forename: R
authors.initials: R
authors.lastname: De Coster
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors; D002460:Cell Line; D002822:Choriocarcinoma / Q000201:enzymology*; D005260:Female; D006801:Humans; D007536:Isomerism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011247:Pregnancy; D014183:Transplantation, Heterologous; D014230:Triazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000201:enzymology*
chemical_list: D047072:Aromatase Inhibitors; D014230:Triazoles; C060523:vorozole