Early lesions in experimental bladder cancer: scanning electron microscopy of cell surface markers

The administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) at a dose of 0.2% of the diet to male Fischer rats results in the appearance of urinary bladder epithelial lesions progressing from hyperplasia to invasive transitional cell carcinomas. These progressive epithelial alterations have been observed by scanning electron microscopy at 2-week intervals with special attention paid to cells covering the luminal surface. After 2 to 4 weeks of FANFT administration there is mild pleomorphism and moderate swelling of the surface cells giving a cobblestone appearance. The normal pattern of microridges of superficial transitional cells is still present, although occasional cells by 4 weeks of FANFT feeding are covered by small uniform microvilli. By 6 weeks these changes are more extensive and more cells are covered with uniform microvilli. By 8 weeks, cells covered with pleomorphic microvilli are found in discrete foci, and by 10 weeks nodular or papillary lesions are present. The 2- and 4-week lesions regress to normal within 2 to 4 weeks of discontinuing FANFT administration, and the 6- and 8-week lesions regress toward normal in 4 to 6 weeks of being fed control diet. The 6-week lesions have regressed entirely to normal 44 weeks after FANFT was stopped, but the 8-week lesions have progressed to moderate or marked hyperplastic lesions by 42 weeks of control diet with pleomorphic cells covered with pleomorphic microvilli. The results of this study suggest that lesions are reversible up to and including 6 weeks of 0.2% FANFT in the diet, and that, by 8 weeks of 0.2% FANFT, irreversible lesions result which do not revert to normal after 42 weeks of control diet.