Time-dependent promotion activity of 17 beta-estradiol on uterine carcinogenesis in mice initiated with N-ethyl-N-nitrosourea

The time-dependent promotion activity of 17 beta -estradiol (E-2) by initia tion with N-ethyl-N-nitrosourea (ENU) on induction of mouse uterine endomet rial proliferative lesions was examined. Illumination-induced persistent es trous female CD-1 mice were divided into five groups at 9 weeks of age. At 10 weeks of age, mice in all groups (n = 25) were given a single intra-uter ine administration of ENU (50 mg/kg), dissolved in polyethylene glycol. Ani mals in Groups 2 to 5 were then implanted s.c. with an E-2 pellet at 9, 11, 14 and 17 weeks of age. The implants were left in place for 8 weeks and th en taken out. At the termination of the experiment (week 15 after the ENU-t reatment), all surviving mice were killed and the development of uterine pr oliferative lesions were assessed. All groups demonstrated endometrial hype rplasias and adenocarcinomas and the incidences of the latter in ENU plus E -2 treated animals (Groups 2 to 5; 36, 48, 35 and 36%, respectively) were s ignificantly higher compared to 8% for Group 1, without any variation with the age at E-2 treatment. However, the incidences of adenocarcinomas plus s evere hyperplasias increased from Groups 1 to 5 (28, 40, 56; P < 0.05, 61; P < 0.05 and 80%; P < 0.01, respectively), indicating that promotion effect s of E-2 on induction of uterine proliferative lesions in the uterine endom etrium become more pronounced with the interval after ENU initiation. (C) 2 001 Elsevier Science Ireland Ltd. All rights reserved.