High-yield Induction of Uterine Endometrial Adenocarcinomas in Donryu Rats by a Single Intra-uterine Administration of N-Ethyl-N-nitro-N-nitrosoguanidine via the Vagina

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Abstract
A total of 130 female Donryu rats (10‐week‐old) were divided into two groups; 80 animals in the experimental group were given a single intra‐uterine administration of 20 mg/kg N‐ethyl‐N‐nitro‐N‐nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG) via the vagina without laparotomy, and 50 animals in the control group received PEG alone in the same manner. Small numbers of animals in both groups were killed at 3, 6, 9 and 12 months after ENNG treatment for sequential histological and endocrinological examination, and at 12.5 experimental months (15 months of age) all survivors were killed. At the termination, endometrial adenocarcinomas were present in 49% of the experimental group, compared to 0% in the control group. Severe endometrial hyperplasias were also found only in the experimental group and sequential histological examination showed first appearance of hyperplasia at 6 months and adenocarcinoma at 9 months. No tumors other than uterine carcinomas were induced by ENNG and the carcinogen treatment did not affect the endocrine environment of rats, persistent estrus appearing at 6 months after the start and increasing with age in both groups. The estradio‐17β:progesterone (E:P) ratio was also increased after 6 months, with further elevation at 12 months to about 8 times higher than the level at 6 months. These results indicate that an increased E:P ratio might act as a promoter of development of endometrial proliferative lesions initiated by ENNG in this rat strain. The study indicates that the present simple method using Donryu rats provides a good animal model for endometrial adenocarcinoma development in women.