Sequential changes of mouse bladder epithelium during induction of invasive carcinomas by N-butyl-N-(4-hydroxybutyl)nitrosamine.

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.