Morphology, classification and histogenesis of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced carcinomas in the urinary bladder of rats.

The aim of the experiments was to determine whether the various types of carcinomas found in the human urinary bladder were reproducible in animals. We added n-butyl-n-(4-hydroxybutyl)-nitrosamine at a dose of 20 mg/kg/day to the drinking water of 177 female Wistar rats for a period of 40 to 150 days. After a total experimental time of between 150 and 250 days the animals were sacrified. The spectrum of carcinomas induced, includes all the types known to occur in man. The various tumor types occurred with the same frequency as in man and exhibited the same growth patterns. Variously differentiated papillary and non-papillary transitional cell carcinomas comprised 88.8% of tumors registered. 5.1% were keratinized and nonkeratinized squamous cell carcinomas, 2.2% adenocarcinomas. 1.1% were undifferentiated carcinomas and 2.8% were carcinomas of the mixed type with squamous cell and transitional cell differentiation. Histogenetically adenocarcinomas were found to originate from glandular metaplasia and squamous cell carcinomas from squamous metaplasia within completely developed transitional cell carcinomas. Furthermore it was possible to induce proliferative lesions such as von Brunn's nests, cystitis cystica and cystitis glandularis. However, we found no clues to substantiate the development of adenocarcinomas from these proliferative lesions, or for that matter squamous cell carcinomas from squamous metaplasia of the otherwise unchanged urothelium. The present experimental model seems particulary suited for the search of further information regarding the development of tumors in the human bladder.