Effects of alpha-difluoromethylornithine on initiation and promotion of urinary bladder carcinogenesis in a heterotopically transplanted rat urinary bladder.

We previously demonstrated that repeated intravesical instillation of DFMO, an irreversible inhibitor of ornithine decarboxylase, inhibits (or retards) urinary bladder carcinogenesis in rats. The present investigation was conducted to determine if high intraluminal concentration of DFMO alters initiation by MNU and to determine if DFMO inhibition is due to arrest of tumor progression or simply retardation of the tumor development. Results showed that the inhibitory effects demonstrated by DFMO treatment during the early phase of study disappeared as the observation period was extended. Failure to suppress tumor development might be due to failure to control intracellular polyamine levels below the critical level and this failure in turn might be due to the rapid fall of intravesical DFMO concentration following instillation.