Influence of various prostaglandin synthesis inhibitors on DMH-induced rat colon cancer

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Abstract
To evaluate the influence of inhibitors of prostaglandin synthesis on the incidence of DMH[dimethylhydrazine]-induced colon cancer, 90 male Sprague-Dawley rats were randomly assigned to: indomethacin 20 mg/l drinking water, meclofenamate 50 mg/l drinking water or normal drinking water (control group). DMH was given by weekly s.c. injections (20 mg/kg body wt) during the first 20 wk. Thirty-two weeks after the start of treatment and carcinogen exposure, the animals were killed and examined for the number, size, location and spread of intestinal tumors. Colon cancer incidence was significantly lower in animals receiving indomethacin (56%) compared with the control group (88%) and with the meclofenamate group (90%) (P < 0.005). The corresponding figures for tumors in the small intestine were 31, 46 and 35%, respectively. The tumors in indomethacin-treated animals did not differ in number, size, location or spread from tumors of the other group, suggesting that indomethacin might influence the carcinogenic process itself, rather than the natural course of the established disease. Indomethacin significantly reduces the incidence of large-bowel cancer in this animal model, and this observation may have some potential for future chemopreventive studies in human high-risk groups (e.g., ulcerative colitis, familial polyposis).