Chemopreventive effect of JTE-522, a selective cyclooxygenase-2 inhibitor, on 1, 2-dimethylhydrazine-induced rat colon carcinogenesis.
Selective COX-2 inhibitors have been suggested to be an effective strategy in the prevention of colon cancer without the adverse side effects of non-selective, nonsteroid anti-inflammatory drugs. The present experiment was designed to assess the potential chemopreventive properties of JTE-522, a new selective cyclooxygenase-2 inhibitor, on the induction of 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF), a marker of rat colon carcinogenesis. A total of 80 male F344 rats were treated with 3 or 10 mg/kg of body weight JTE-522 or vehicle by oral gavage five times weekly from the start of the experiment. One week later, rats received s.c. injections of saline or 20 mg/kg of body weight DMH once weekly for four successive weeks. At the end of 12 weeks after the start of experiment, all rats were sacrificed and colons were evaluated for ACF. 10 mg/kg JTE522 significantly suppressed the total ACF/colon. No inhibitory effect was observed in the 3 mg/kg JTE-522 treatment group. This result suggests that JTE-522 possesses chemopreventive activity against colon carcinogenesis.
Wei
Min
M
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Morimura
Keiichirou
K
Wanibuchi
Hideki
H
Shen
Jun
J
Doi
Kenichiro
K
Mitsuhashi
Makoto
M
Moku
Masaharu
M
Salim
Elsayed I
EI
Fukushima
Shoji
S
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D001557:Benzenesulfonates / Q000627:therapeutic use*; D001973:Bromodeoxyuridine; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D018450:Disease Progression; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D010080:Oxazoles / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D011916:Rats, Inbred F344; D000096926:Benzenesulfonamides
D019813:1,2-Dimethylhydrazine; D001557:Benzenesulfonates; D001973:Bromodeoxyuridine; D002273:Carcinogens; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D010080:Oxazoles; D011451:Prostaglandin-Endoperoxide Synthases; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides