INHIBITION OF DEVELOPMENT OF METHYLNITROSOUREA-INDUCED RAT COLONIC TUMORS BY PERORAL ADMINISTRATION OF INDOMETHACIN

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 73  (3) , 377-381
Abstract
The nonsteroid antiinflammatory drug indomethacin, a prostaglandin synthesis inhibitor, inhibited the development of carcinogen-induced large bowel carcinomas in rats. CD-Fischer rats were given carcinogenic pretreatment with intrarectal instillation of 2 mg of methylnitrosourea 3 times a wk from the 1st to the 5th wk, in order to produce large bowel tumors. Thereafter, peroral administration of a high or low dose of indomethacin dissolved in drinking water (20 .mu.g or 10 .mu.g indomethacin/ml tap water) for 15 wk was started at the 11th wk, before the tumors developed. At autopsy in the 26th wk just after the completion of the 15-wk treatment, the incidence of developing large bowel tumors was significantly reduced in treated rats, compared to untreated control rats; 17% or 14% vs. 67%. However, at autopsy in the 36th wk, 10 wk after cessation of the treatment, the development of tumors in treated rats was significantly increased. Thus, indomethacin inhibited the development of methylnitrosourea-induced large bowel tumors in rats. The effectiveness of peroral administration of indomethacin was comparable to that of i.p. administration. It is postulated that treatment with this drug may effectively prevent the development of large bowel cancer in patients at high risk.