STUDIES ON THE MECHANISM OF UTERINE CARCINOGENESIS USING TWO-STAGE MOUSE CARCINOGENESIS PROTOCOL

In this studies，a two-stage mouse uterine carcinogenesis method by a initiator/N-ethyl-N'-nitro-N-nitrosoguanidine（ENNG） and promoter/17β-estradiol (E - D22 - D2) was established，以及tamoxifen （TAM）和ascorbic acid (ASA) on endometrial adenocarcinomadevelopment was investigated using this model，in addition to promotion effects of E - 22 E - D2 and it's metabolite-steroids in. High incidence ofadenocarcinomas was observed in ENNG combined with E - 22 - D2 group animals at the termination ofthe experiment （week 15 after the ENNG-treatment）but ENNG + E D22 + TAM-treated group could not see any promotion effect. TAM decreased uterineweight compared with control.这些结果indicate that administration of TAM inhibit thepromoting effect of E - 22 E - D2 on ENNG-induced uterine carcinogenesis，TAM affecting as an anti-estrogen. On the other hand，incidence of adenocarcinomas in the ENNG + E - D22 - D2 + ASA group was 1.5 time higher thanASA-untreated group, but…More being not significant. It is known that ascorbic acid （0.3% in）inhibit the promoting effect of estradiol dipropionate on uterine sarcomadevelopment by 1,2-dimethylhydrazine in CBA mice. Thus，ASA inhibited promoting effect of E - 22 E - D2 on uterine sarcoma development，but activated adenocarcinoma. This indicate，estrogen may have different promotion mechanism between uterine adenocarcinoma and sarcoma.Promotion effects of E - 22 E - D2 and its metabolite-steroids on ENNG-initiated mice were examined.High incidences of adenocarcinoma were observed in mice treated with E E D21 E E D2E D22 E D2 and 17-epi E D23 E D2 steroids，medium incidences were observed in animals treated with E D23 D2，16α-hydroxy and 16β-hydroxy E D21 E D2 steroids. 2- hydroxy and methoxy steroids did not affected.These results indicate that promotion effects of E - 22 E - D2 metabolite-steroids on uterinecarcinogenesis in ENNG-initiated mice were shown by metabolite products to 16α-OH and 16β-OHsteroids, but not to 2β-OH steroids. Less

In this studies, a two-stage mouse uterine carcinogenesis method by a initiator/N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and promoter/17β-estradiol (EィイD22ィエD2) was established, and also the effects of tamoxifen (TAM) and ascorbic acid (ASA) on endometrial adenocarcinoma development was investigated using this model, in addition to promotion effects of EィイD22ィエD2 and it's metabolite-steroids in. High incidence of adenocarcinomas was observed in ENNG combined with EィイD22ィエD2 group animals at the termination of the experiment (week 15 after the ENNG-treatment), but ENNG + EィイD22ィエD2 + TAM-treated group could not see any promotion effect. TAM decreased uterine weight compared with control. These results indicate that administration of TAM inhibit the promoting effect of EィイD22ィエD2 on ENNG-induced uterine carcinogenesis, TAM affecting as an anti-estrogen. On the other hand, incidence of adenocarcinomas in the ENNG + EィイD22ィエD2 + ASA group was 1.5 time higher than ASA-untreated group, but … More being not significant. It is known that administration of ascorbic acid (0.3% in drinking water) inhibit the promoting effect of estradiol dipropionate on uterine sarcoma development by 1,2-dimethylhydrazine in CBA mice. Thus, ASA inhibited promoting effect of EィイD22ィエD2 on uterine sarcoma development, but activated adenocarcinoma. This indicate, estrogen may have different promotion mechanism between uterine adenocarcinoma and sarcoma. Promotion effects of EィイD22ィエD2 and its metabolite-steroids on ENNG-initiated mice were examined. High incidences of adenocarcinoma were observed in mice treated with EィイD21ィエD2, EィイD22ィエD2 and 17-epi EィイD23ィエD2 steroids, medium incidences were observed in animals treated with EィイD23ィエD2, 16α-hydroxy and 16β-hydroxy EィイD21ィエD2 steroids. 2-Hydroxy and methoxy steroids did not affected. These results indicate that promotion effects of EィイD22ィエD2 metabolite-steroids on uterine carcinogenesis in ENNG-initiated mice were shown by metabolite products to 16α-OH and 16β-OH steroids, but not to 2β-OH steroids. Less