HISTOPATHOLOGICAL ANALYSIS OF PRENEOPLASTIC CHANGES DURING N‐BUTYL‐N‐(4‐HYDROXYBUTYL)‐ NITROSAMINE‐INDUCED URINARY BLADDER CARCINOGENESIS IN RATS

Sequential microscopic alterations of the urinary bladder epithelium during carcinogenesis were examined in rats after oral administration of 0.01% or 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN). Simple hyperplasia appeared after 4 weeks of BBN administration. This regressed by 12 weeks after BBN discontinuation but reappeared focally in some areas after 20 weeks and persisted to the termination of the experiment. Preneoplastic papillary or nodular hyperplasia appeared earlier and more frequently in rats treated with 0.05% BBN than in those treated with 0.01%, but these lesions regressed gradually during a prolonged observation period after BBN was discontinued. These results suggest that 2 types of papillary or nodular hyperplasias exist, one reversible and the other irreversible. Tumors appeared earlier in rats treated with 0.05% BBN than in those with 0.01% BBN.