Correlation of urothelial morphologic characteristics with the development of bladder carcinomas in BALB/c female mice administered 2-acetylaminofluorene.

Urinary bladders from 6909 of 24,172 control or 2-acetylaminofluorene (2-AAF) treated female BALB/c mice were examined histopathologically. Dietary doses of 2-AAF ranged from 75 to 150 p.p.m. for up to 33 months. Urinary bladder epithelial hyperplasia, vacuolization, and inflammation were frequent observations in treated animals and showed a positive correlation with dose level and length of administration of 2-AAF. Concretions were infrequently found and occurred only in controls. Squamous metaplasia, ulceration, and lymphocytic accumulations were infrequently noted but gave some indication of a positive correlation with 2-AAF dose level. Vacuolization was always associated with hyperplasia and/or bladder tumors. Observations on the concurrence of hyperplasia, vacuolization, and neoplasia suggest that both hyperplasia and vacuolization may be precursors of neoplasia. While inflammation was infrequently noted in non-tumor-bearing animals, greater than 90% of the time it was seen in association with tumors and appears to be a response of the bladder to tumor progression.