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The patterns of epithelial proliferation in the urinary bladder during carcinogenesis were examined sequentially in rats given drinking water supplemented with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 12 weeks and then water without BBN for 18 weeks. Animals received 120 micrograms of bromodeoxyuridine (BrdU) per hour continuously via an osmotic minipump for 4 days before sacrifice and labeled cells were detected immunohistochemically using monoclonal antibody against BrdU. Two types of BBN-induced epithelial lesions were distinguishable: reversible changes characterized by proliferation of basal cells only, and irreversible changes with high and irregularly distributed incorporation of label throughout the epithelium. Simple hyperplasia, and papillary or nodular hyperplasia consisted of areas of reversible and/or irreversible changes, whereas papilloma and cancer consisted of areas of irreversible changes.

Patterns of epithelial proliferation revealed by continuous administration of bromodeoxyuridine during urinary bladder carcinogenesis in rats.