Aromatase inhibition by R 83 842, the dextro isomer of R 76 713, in JEG-3 choriocarcinoma grown in ovariectomized nude mice.

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.