Histologic and histochemical preneoplastic changes in the bladder mucosae of dogs given 2-naphthylamine.

So that the earliest morphologic changes produced in dog bladders by a bladder carcinogen could be detected, 25 mg 2-naphthylamine/kg was given daily to dogs for 1, 6, and 36 weeks. Among early changes observed in some, but not all, dogs at 1 and 6 weeks were a loss of the bladder luminal membrane, hyperplasia of the epithelium, and lymphocytic infiltration of the submucosa. These changes were also present, to a more severe degree, in all dogs at 36 weeks. A more advanced preneoplastic change observed only at 36 weeks was a scalloped appearance of the normally straight basal cell line due to the beginning of nodule formation of the hyperplastic epithelial cells (von Brunn's epithelial nests). Histochemically, the alkaline phosphatase activity was altered from the normally regular, dense staining of the basal cell layer to a weaker, intermittent staining. No tumors were observed. Of the dogs given the same dose of 2-naphthylamine for 26 weeks and then kept for 3 years before being killed, 2 dogs had normal bladders but the other 2 had epithelial carcinomas.