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 inhibitor, nimesulide (NIM), against the development of rat superficial urinary bladder carcinomas after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. Six-week-old Fischer 344 male rats were given 0.05% BBN in their drinking water for 8 weeks, followed by diets 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 0.75 +/- 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 indicate clear chemopreventive potential of a selective cyclooxygenase-2 inhibitor against postinitiation development of superficial rat urinary bladder carcinomas.
Okajima
E
E
Department of Oncological Pathology, Cancer Center, Nara Medical University, Japan.
Denda
A
A
Ozono
S
S
Takahama
M
M
Akai
H
H
Sasaki
Y
Y
Kitayama
W
W
Wakabayashi
K
K
Konishi
Y
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004435:Eating / Q000187:drug effects; D015994:Incidence; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013449:Sulfonamides / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D002085:Butylhydroxybutylnitrosamine; C012655:nimesulide