Time- and dose-dependent induction of invasive urinary bladder cancers by N-ethyl-N-(4-hydroxybutyl)nitrosamine in B6C3F1 mice.

A sequential investigation of N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) bladder carcinogenesis was performed in male B6C3F1 mice maintained ad libitum on tap water containing 0.025% EHBN for 4, 12, 20, 28 and 36 weeks. A total of 81 invasive tumors, comprising 55 squamous cell carcinomas (SCCs) (68%), 25 transitional cell carcinomas (TCCs) (31%) and 1 adenocarcinoma (1%) were found. Of these, 23 (22 SCCs and 1 TCC) demonstrated invasion to the prostate, 3 metastasized to the lung, and 2 spread by peritoneal seeding. The anaplastic grade and extent of invasion of the SCCs significantly exceeded those of the TCCs. The results suggested a histogenetic pathway from simple dysplasia through papillary or nodular dysplasia and/or carcinoma in situ to eventual development of invasive carcinomas.