Immunohistochemical study of keratin in proliferative bladder epithelium induced by freezing, cyclophosphamide or N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in the rat

The distribution of intracellular keratin proteins was examined in a variety of urinary bladder lesions of the rat using the immunoperoxidase staining technique. In ethanol-fixed sections, the normal epithelium was strongly positive for keratin staining. Focal regenerative hyperplasia of the bladder epithelium induced by freezing exhibited relatively weak staining. However, diffuse regenerative hyperplasia induced by a single intraperitoneal injection of cyclophosphamide (CP) showed an intensely positive reaction throughout the epithelium. Of the sections fixed with Bouin's solution, the staining reaction was drastically reduced in the normal bladder and the staining was totally negative in the regenerative hyperplasia caused by freezing. Simple hyperplasia induced by a 4-week feeding of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as 0.2% of the diet exhibited strong reactivity, and nodular and papillarly hyperplasia induced by a 10-week feeding of FANFT was also positive for keratin throughout the lesions. In contrast to the preneoplastic lesions, FANFT-induced transitional cell carcinoma showed differential staining within the tumors. These results suggest that different keratin expression is involved in the proliferative bladder lesions induced mechanically by freezing and chemically by CP or by the carcinogen FANFT.