RAPID INDUCTION OF ENDOMETRIAL CARCINOMA IN ICR MICE TREATED WITH N-METHYL-N-NITROSOUREA AND 17-BETA-ESTRADIOL

The present study was undertaken to develop an animal model for endometrial neoplasms. A total of 107 female ICR mice, 10 weeks of age, were used and treated as follows: Group 1 (31 mice) was given intravaginal instillation of N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body wt.) once a week for three weeks and then fed diet containing 5 ppm 17-beta-estradiol (E2) for 20 weeks, starting one week after the last exposure to MNU. Group 2 (30 mice) was given MNU alone. Group 3 (31 mice) was given E2 diet alone. Group 4 (15 mice) was fed the basal diet alone and served as the untreated control. At the termination of the experiment (week 23), all surviving mice were killed. Histopathological examination revealed that adenocarcinomas in the uterine corpus developed in mice of Groups 1-3, with a high incidence of endometrial hyperplasia. The incidence of endometrial carcinomas in Group 1 (15/31, 48%) was significantly higher than in Group 2 (2/29, 7%, P < 0.001) or Group 3 (7/31, 23%, P < 0.01). In the uterine cervix, small numbers of squamous cell carcinomas and preneoplastic lesions (dysplasias and hyperplasias) were also present in mice of Groups 1-3. In Groups 1 and 3, an increased E2/progesterone (P) ratio was observed. Thus, the results indicated that this medium-term model for endometrial neoplasms is useful for studying the pathogenesis of endometrial cancer and that an increased E2/P ratio is an important factor for the development of endometrial adenocarcinoma.