Comparison of uroplakin expression during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats and mice

The expression of uroplakins, the tissue-specific and differentiation-depen dent membrane proteins of the urothelium, was analyzed immunohistochemicall y in N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-treated rats and mice duri ng bladder carcinogenesis. Male Fischer 344 rats were treated with 0.05% BB N in the drinking water for 10 wk and were euthanatized at week 20 of the e xperiment. BBN was administered to male B6D2F, mice; it was either provided at a rate of 0.05% in the drinking water (for 26 wk) or 5 mg BBN was admin istered by intragastric gavage twice weekly for 10 wk, followed by 20 wk wi thout treatment. In rats, BBN-induced, noninvasive, low-grade, papillary, t ransitional cell carcinoma (TCC) showed decreased uroplakin-staining of cel ls lining the lumen but showed increased expression in some nonluminal cell s. In mice, nonpapillary, high-grade dysplasia, carcinoma in situ, and inva sive carcinoma were induced. There was a marked decrease in the number of u roplakin-positive cells lining the lumen and in nonluminal cells. This occu rred in normal-appearing urothelium in BBN-treated mice and in dysplasic ur othelium, in carcinoma in situ, and in invasive TCC. The percentage of urop lakin-positive nonluminal cells was higher in control mice than in rats, bu t it was lower in the mouse than in the rat after BBN treatment. Uroplakin expression was disorderly and focal in BBN-treated urothelium in both speci es. These results indicate that BBN treatment changed the expression of uro plakins during bladder carcinogenesis, with differences in rats and mice be ing related to degree of tumor differentiation.