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
E. Okajima et al., 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, Cancer research, 58(14), 1998, pp. 3028-3031
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.