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

在本研究中，由启动者/N-ethyl-N '-nitro-N-nitro-N-nitrooguanidine（ENNG）和promoter/17β-estradiol（Ei-D22-D2）开发的两级小鼠甲状腺素生成方法也使用该模型研究了Ei-D22-E-D2和它的代谢-类固醇的影响。High incidence of adenocarcinomas was observed in ENNG combined with E-D22 E-D2 group animals at the termination of the experiment （week 15 after the ENNG-treatment）， but ENNG + E-D22 E-D2 + TAM-treated group could not see any promotion effect。TAM减少的uterine weight与控制相比较。这些结果表明了TAM的管理抑制了E-E-D22-E-D2上的ENNG-induced uterine carcinogenesis， TAM影响作为反estrogen。在其他方面，ENNG + E-D22-E-D2 + ASA组的腺癌发生率比ASA未覆盖组高1.5小时，但 ... More 这并不意味着什么。众所周知，糖基酸的管理（在水中的0.3%）通过CBA老鼠的开发，抑制了雌二醇二丙酯对甲状腺素的推广效应。Thus， ASA inhibited promoting effect of Ey D22 Ey D2 on uterine sarcoma development， but activated adenocarcinoma。根据这一说法，雌激素可能在甲状腺腺癌和肉瘤之间有不同的促销活动。在ENNG-initiated mice were examined上的Promotion effects of E-D22和its metabolite-steroids。adenocarcinoma在老鼠处理时观察到E-D21-E-D2，E-D22-E-D2和17-epi E-D23-D2类固醇，中基因在动物处理时观察到E-D23-D2、16-羟和16-羟E-羟D-D21-羟D-D2类固醇。2-羟基和甲氧基类固醇并不受影响。这些结果表明，在ENNG-启动的老鼠中显示出代谢产品对E-D22-D2代谢类固醇的促进影响，但不影响到2β-OH类固醇。Less（低）

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