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The purpose of this study was to clarify whether the anti-angiogenesis drug TNP-470 may exert inhibitory effects on rat urinary bladder papillomatosis. A total of 46, six-week-old, male F344/DuCrj rats were used. In groups 1 and 2, 20 male F344/DuCrj rats each underwent intravesical instillation of 5 beads (1.5 mm diameter) via the abdomen to cause mechanical irritation. Group 3 was included as a control group without beads. Rats in group 1 were then treated with subcutaneous (s.c.) injections of TNP-470 at the dose of 30 mg/kg body wt, 3 times a week for 4 weeks. The vehicle alone was injected s.c. for groups 2 and 3. Subgroups of animals (10 rats each in groups 1 and 2, and 3 in group 3) were killed at weeks 2 and 4 after the beginning of the experiment. Urinary bladder weights of rats treated with intravesical instillation of beads (groups 1 and 2) were significantly increased compared with normal control rats (group 3). There was no difference between urinary bladder weights and calculi weights of groups 1 and 2 at 4 weeks. Histologically, the urinary bladder epithelium of rats suffering mechanical irritation due to the beads (groups 1 and 2) was significantly hyperplastic, demonstrating papillomatosis. There were no significant differences in the degrees or extents of epithelial lesions between groups 1 and 2. Furthermore, elevation of ODC and SAT activities, biomarkers of cell proliferation, in the epithelium was similar in both groups. TNP-470 thus did not inhibit epithelial proliferation in the urinary bladder in this experiment.

Lack of Inhibitory Effects of an Anti-angiogenesis Drug, TNP-470, on Rat Urinary Bladder Papillomatosis Induced by Mechanical Stimulation.