Dose-Response Relationships of the Bladder Tumorigen 2-Naphthylamine: A Study in Beagle Dogs

Tumors of the urinary bladder were induced in dogs given varying daily doses of 2-naphthylamine orally for different periods. The spectrum of pathology extended from preneoplastic hyperplasia to invasive squamous carcinoma. The morphology of the induced tumors was compared with material obtained in 25 cases of spontaneous canine bladder carcinoma. Although a dose-response relationship was apparent, it was not a linear function. The data indicated that the total amount of tumorigen required for tumor induction was less when a small daily dose (6.25 mg/kg) was given for 24–30 months than when a larger daily dose (25 or 50 mg/kg) was given for 9–18 months. The data suggest that a power of the treatment time (tn) was a component in the dose-response relationship.