Modifying Effects of Genistein, 4-Nonylphenol and Methoxychlor on N-ethyl-N-nitrosourea-induced Uterine Carcinogenesis in RasH2 Transgenic Mice Harboring a Human Prototype C-Ha-ras Gene
Watanabe Takao1), Ueda Makoto2), Yasuhara Kazuo2), Onodera Hiroshi2), Hirose Masao2), Mitsumori Kunitoshi1)2)
1) Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
2) Division of Pathology, National Institute of Health Sciences
(Received 4-Apr-2002)
(Accepted 25-Jun-2002)
Abstract: In our previous study, uterine endometrial atypical hyperplasias and adenocarcinomas were induced in female transgenic mice harboring human proto type c-Ha-ras gene (rasH2 mice) within 22 weeks by a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU). In order to clarify the modifying effects of genistein (GE), 4-nonylphenol (NP), and methoxychlor (MXC) on uterine endometrial carcinogenesis, female rasH2 mice received an intraperitoneal injection of 120 mg/kg body weight (bw) of ENU, followed by no further treatment, diet containing 250 ppm GE, diet containing 250 ppm NP, or diet containing 1,000 ppm MXC for 24 weeks. Uterine proliferative lesions that were observed in treated groups were composed of endometrial hyperplasias, atypical hyperplasias of the endometrium, and adenocarcinomas. The incidence of adenocarcinomas in the ENU alone, ENU+GE, ENU+NP, and ENU+MXC groups was 55.6, 57.1, 47.1, and 0%, respectively, that in the ENU+MXC group being significantly depressed as compared to the ENU alone group (p<0.05). The incidence of atypical hyperplasias in the ENU+MXC group was also decreased. The results in the present study suggest that 1,000 ppm MXC, but not GE and NP, shows an inhibitory effect on the development of uterine adenocarcinomas in rasH2 mice initiated with ENU.
Key words: N-ethyl-N-nitrosourea, genistein, nonylphenol, methoxychlor, uterine carcinogenesis, rasH2 mice
