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Sequential Changes of Mouse Bladder Epithelium during Induction of Invasive Carcinomas by N-Butyl-N-(4-hydroxybutyl)nitrosamine¹

Urology Division [M. O., T. K., Y. N.] and Biochemistry Division [S. S., T. S.], National Cancer Center, Tokyo 104; Department of Pathology [S. F.], Nagoya City Medical School, Nagoya 467; and Department of Urology [T. N.], Faculty of Medicine, University of Tokyo, Tokyo 113, Japan

Invasive carcinoma of the bladder in humans shows aggressive growth with poor prognosis. Little is known about its preceding lesions. Sequential changes of the bladder epithelium following administration of N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) were studied in mice. Female C3H/He mice were divided into 4 groups. Three groups were given 0.05, 0.01, and 0.005% concentrations of BHBN, respectively, in their drinking water, and the control group was given tap water. The mice were killed at regular intervals over a period of 26 weeks, and their bladder epithelium was examined histologically. Dysplasia, carcinoma in situ, and invasive carcinoma were observed sequentially in the groups treated with BHBN, and the incidences of dysplasia, carcinoma in situ, and invasive carcinoma were dependent on the dose of BHBN. The data indicate that bladder carcinoma in mice is a good model of invasive bladder carcinoma in humans, although it is not fully compatible with the human model because of the complete absence of metastases.

¹ This work was supported by a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control and also by Grants-in-Aid from the Ministry of Health and Welfare (58-5) and the Ministry of Education, Science, and Culture (58010062) of Japan.

² To whom requests for reprints should be addressed, at the Urology Division, National Cancer Center, Tsukiji 5-1-1. Chuo-ku, Tokyo 104, Japan.

Received 8/26/85. Revised 12/ 4/85. Accepted 12/27/85.

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