Rapid induction of uterine endometrial proliferative lesions in transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice) given a single intraperitoneal injection of N-ethyl-N-nitrosourea.
In our previous study, uterine endometrial stromal sarcomas and atypical hyperplasias of the endometrial glands were induced in heterozygous p53 deficient mice (p53 (+/-) mice) of the CBA strain given a single dose of N-ethyl-N-nitrosourea (ENU). In order to clarify whether uterine tumors can be induced in transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice) that are very susceptible to genotoxic carcinogens, rasH2 mice and their wild-type littermates received an intraperitoneal injection of 120 or 0mg/kg body weight of ENU followed by no further treatment for 22 weeks. Eighteen and 94% of ENU-treated rasH2 mice had uterine endometrial adenocarcinomas and atypical hyperplasias, respectively. Other malignant and benign tumors such as lung alveolar/bronchiolar adenomas and carcinomas, forestomach squamous cell papillomas and carcinomas, splenic hemangiomas/sarcomas, skin papillomas, malignant lymphomas and harderian gland adenomas were also observed in ENU-treated rasH2 mice. The result in the present study suggests that female rasH2 mice are very susceptible to uterine carcinogenesis, providing a useful model for ENU-induced uterine epithelial tumors.
Watanabe
Takao
T
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan.
Kashida
Yoko
Y
Yasuhara
Kazuo
K
Koujitani
Takatoshi
T
Hirose
Masao
M
Mitsumori
Kunitoshi
K
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D007274:Injections, Intraperitoneal; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D017354:Point Mutation
D000477:Alkylating Agents; D005038:Ethylnitrosourea