CHEMOPREVENTIVE EFFECTS OF NIMESULIDE, A SELECTIVE CYCLOOXYGENASE-2 INHIBITOR, ON THE DEVELOPMENT OF RAT URINARY-BLADDER CARCINOMAS INITIATED BY N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE

The chemopreventive potential of a selective cyclooxygenase 2 inhibito r, nimesulide (NIM), against the development of rat superficial urinar y bladder carcinomas after initiation with N-butyl-N-(4-hydroxybutyl)n itrosamine (BBN) was examined. Six-week-old Fischer 344 male rats were given 0.05% BBN in their drinking water for 8 weeks, followed by diet s supplemented with 0, 100, 200, or 400 ppm NIM for 12 weeks, and they were then sacrificed. NIM decreased, in a dose-dependent manner, the incidence of transitional cell carcinoma (TCC) to 12 of 20 (60.0%), 8 of 16 (50.0%), and 5 of 19 (26.3%) and the multiplicity of TCCs to 0.7 5 +/- 0.79, 0.56 +/- 0.63, and 0.37 +/- 0.78 per rat at 100, 200, and 400 ppm, respectively, as compared with the BBN alone group values of 18 of 20 (90.0%) and 2.35 +/- 1.23. NIM did not significantly. affect the cell differentiation or invasiveness of TCCs. These results indica te clear chemopreventive potential of a selective cyclooxygenase-2 inh ibitor against postinitiation development of superficial rat urinary b ladder carcinomas.