Urothelial Damage and Tumor Initiation by Urinary Metabolites of Sodium o‐Phenylphenate in the Urinary Bladder of Female Rats

Intravesical instillation of 2‐phenyl‐1,4‐benzoquinone (PBQ), a metabolite of sodium o‐phenylphenate (Na‐OPP), at a concentration of 0.1% in saline caused acute epithelial injury, prolonged inflammation and epithelial hyperplasia in female F344 rats. Ten such instillations of PBQ within 5 weeks resulted in the development of preneoplastic lesions of the urinary bladder epithelium when followed by 5% sodium saccharin feeding for 31 weeks. Since neither urothelial damage nor tumor‐initiating activity was observed with either Na‐OPP itself or another metabolite, phenylhydroquinone, PBQ may play an essential role in Na‐OPP urinary bladder carcinogenesis.