| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Midori PATHOLOGY, SASAKI INSTITUTE, RESEARCHER, 病理部, 研究員 (70201861)
ANDO Jin PATHOLOGY, SASAKI INSTITUTE, RESEARCHER, 病理部, 研究員 (10240433)
MAEKAWA Akihiko PATHOLOGY, SASAKI INSTITUTE, HEAD RESEARCHER, 病理部, 部長 (30106182)
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| Research Abstract |
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
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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
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