PROLIFERATIVE LESIONS OF OVIDUCT AND UTERUS IN CD-1 MICE EXPOSED PRENATALLY TO TAMOXIFEN

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age, However, TAM therapy has been shown to result in an increased inciden ce of endometrial carcinoma in women. The present study was designed t o investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring, Progressive proliferative hyperplasia of th e oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also dev eloped progressive proliferative uterine lesions, including moderate/s evere cystic endometrial hyperplasia (34-50%) and polypoid adenomas (2 7-30%) between 53 and 78 weeks, Deciduomas (15%) occurred at young age s (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma , and ovarian granulosa cell tumors (14%), were found between 72 and 7 8 weeks, Our findings thus suggest a strong association between transp lacental TAM and reproductive tract abnormalities in female CD-1 mice.