INHIBITION OF DEVELOPMENT OF METHYLNITROSOUREA-INDUCED RAT COLON TUMORS BY INDOMETHACIN TREATMENT

Abstract

The nonsteroid antiinflammatory drug indomethacin, a prostaglandin synthesis inhibitor, was used in the treatment of carcinogen-induced colonic tumors in rats. CD-Fischer rats were given an intrarectal instillation of methylnitrosourea (2 mg, 3 times per wk from the 1st to 4th week) to produce colonic tumors. Thereafter, a long-term treatment with i.p. injection of indomethacin (2.5 mg/kg body weight, 3 times per wk) was started at the 11th wk, before the tumors developed. At autopsy, after the 15 wk treatment with indomethacin, the colonic tumor incidence was significantly lower in treated rats than in vehicle-treated or untreated control rats. The 10 wk cessation of treatment following this effective dosage led to a rapid development of tumors. In another experimental group of rats in which tumors were detected endoscopically, when treatment was initiated late, at the 26th wk, for 10 wk, tumor incidence and number were not altered. Indomethacin probably inhibited the development of colonic tumors but did not reject or kill the growing tumors. Indomethacin treatment may effectively prevent the development of colonic cancer in patients at high risk of colonic adenomatosis and carcinomatosis.