Rapid induction of bladder cancer in rats with N-methyl-N-nitrosourea I. Histology

A single dose of 2 mg of N -methyl- N -nitrosourea was instilled directly into the urinary bladder of each of 50 male Wistar rats, but despite initial epithelial necrosis followed by hyperplasia none of these developed tumours.

Abstract

A single dose of 2 mg of N-methyl-N-nitrosourea (MNU) was instilled directly into the urinary bladder of each of 50 male Wistar rats. 10 animals were kept for 50 weeks or more after dosing, but despite initial epithelial necrosis followed by hyperplasia none of these developed tumours. In a second series the dose was increased to 3 mg but this proved lethal. In a third series of 100 animals the amount was increased to a total of 6 mg but given as 4 doses over a period of 6 weeks. In this group initial necrosis and stripping of the epithelium was followed by marked hyperplasia leading to papillomas and transitional cell tumours. In addition nests of squamous cells developed early, proliferated rapidly and invaded the sub-mucosa and muscle of the bladder wall to form small squamous tumours on the peritoneal surface. Bladder tumours appeared from 12 weeks on. When examined after 20 weeks all animals had tumours of the urothelium with the exception of one which when killed at 28 weeks, had a grossly hyperplastic epithelium.