Promoting effects of various agents in rat urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine

The effects of various chemicals on the development of neoplastic lesions in the urinary bladder were investigated in male F344 rats given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiator in their drinking water for 4 weeks. The compounds tested, indomethacin, acemetacin, epsilon-aminocaproic acid (EACA), diphenyl, allopurinol and acetaminophen (AAP), were added to the diet or drinking water for 32 weeks, and all animals were killed at the end of week 36. Of the chemicals tested, only diphenyl significantly increased the incidences and average numbers (per 10 cm basement membrane) of papillary or nodular hyperplasias (PN hyperplasia), papillomas and carcinomas of the urinary bladder over those in animals treated with BBN alone. These findings show that diphenyl is a promoter of urinary bladder carcinogenesis in male F344 rats.