EXPRESSION AND LOCALIZATION OF ORNITHINE DECARBOXYLASE IN REVERSIBLE PAPILLOMATOSIS INDUCED BY URACIL IN RAT BLADDER

Direct mechanical irritation by uracil calculi formed following feedin g of 3% uracil in the diet to male rats produces severe papillary hype rplasia (papillomatosis, which is reversible) of bladder epithelium, T o evaluate the mechanism of the appearance of uracil-induced papilloma tosis, we examined the changes of the enzyme activity and the localiza tion of ornithine decarboxylase (ODC), as well as polyamine biosynthes is, and epithelial proliferation, that accompany the sequential bladde r epithelial changes following administration and withdrawal of uracil . Moreover, expression of ODC mRNA was investigated using northern blo tting and localization of ODC mRNA was demonstrated using in situ hybr idization, ODC activity during uracil administration was maintained at a high level compared to that in normal epithelium, but sharply decre ased after cessation of uracil treatment. The accumulation of ODC prot ein was observed in the proliferating bladder epithelium by immunohist ochemical examination and western blotting analysis, and even after ce ssation of treatment, the protein binding to anti-ODC antibody remaine d mildly elevated, Sequential changes of proliferating cell nuclear an tigen (PCNA)-positive cells in the epithelium during the development a nd disappearance of papillomatosis correlated with ODC activity, ODC m RNA was expressed strongly in the proliferating epithelium in rats tre ated with uracil and weakly in normal epithelium, in accordance with t he location of ODC protein. Consequently, our data demonstrate that ce ll proliferation in the development of papillomatosis is closely assoc iated with polyamine metabolism, and moreover suggest that ODC activit y is up-regulated at a posttranslational step.