The effect of four dose levels of
piroxicam administered during different stages of colon
tumor development was studied in male F344 rats to obtain a data base on the efficacy of
piroxicam as an inhibitor of colon
carcinogenesis.
Piroxicam was added at levels of 25, 50, 75, and 150 ppm to the NIH-07 open-formula diet and fed to male F344 rats starting 1, 13, and 23 wk after the
carcinogen administration. At 7 wk of age, while the animals were consuming the control diet, all animals except the vehicle-treated controls were given s.c. injection of
azoxymethane (CAS:25843-45-2; 29.6 mg/kg
body weight, once) to induce intestinal
tumors. Forty wk after AOM injection, all animals were necropsied, and
tumor incidences were compared among the various dietary groups. Colon
tumor incidence (percentage of animals with
tumors) was inhibited in a dose-dependent manner in rats fed the diets containing 25, 50, 75, and 150 ppm
piroxicam starting 1 and 13 wk after
carcinogen treatment. The colon
tumor incidences in animals fed the diets containing 0, 25, 50, 75, and 150 ppm of
piroxicam starting at 1 wk after
carcinogen treatment were 89, 61, 58, 50, and 39%, respectively. When the diets containing 0, 25, 50, 75, and 150 ppm were fed 13 wk after
carcinogen treatment, the colon
tumor incidences were 89, 69, 69, 44, and 33%, respectively. Colon
tumor multiplicity (
tumors/animal;
tumors/
tumor-bearing animal) was also significantly inhibited in animals fed the diets containing 25 to 150 ppm
piroxicam starting 1 and 13 wk after
carcinogen administration. The number of colon
tumors/animal was inhibited by about 80 to 84% in animals fed the 150 ppm
piroxicam diet. When the diets containing different levels of
piroxicam were fed 23 wk after
carcinogen treatment, the colon
tumor incidence was significantly inhibited in animals fed the 75 and 150 ppm
piroxicam diets. The colon
tumor incidences in animals fed the diets containing 0, 25, 50, 75, and 150 ppm were 89, 78, 67, 64, and 64%, respectively. The colon
tumor multiplicity (colon
tumors/animal) was slightly but significantly inhibited in animals fed the diets containing 25 to 150 ppm
piroxicam. The results of this study demonstrate that increasing levels of
piroxicam in the diet, when fed 1 or 13 wk after
carcinogen insult, inhibit colon
tumor incidence in a dose-dependent manner.