Reduction of acetoxymethyl-methylnitrosamine-induced large bowel cancer in rats by indomethacin.

The nonsteroid anti-inflammatory drug indomethacin, a potent prostaglandin synthesis inhibitor, may play a role in preventing chemically-induced large bowel cancer development in rats. 250 male Sprague-Dawley rats were given weekly intrarectal doses of 2 mg/kg body weight of acetoxymethyl-methylnitrosamine (AMMN) in the first 10 weeks of the experiment to induce large bowel tumors. Experimental groups received a 0.001% aqueous solution of indomethacin ad libitum as drinking water for different time intervals. At autopsy in week 21, the indomethacin treatment in the first and second 10-week periods, or only in the second 10-week period significantly reduced the number of large bowel tumors compared to non-treatment control groups, while the treatment in the first 10-week period alone did not affect the tumor development. It was observed at autopsy in week 31 that the 10-week cessation of treatment after the effective treatments permitted the growth of tumors, but the treatment in the first and second 10-week periods was effective enough to suppress tumor appearance compared to other groups. It can be concluded that indomethacin has an antiproliferative activity on large bowel carcinogenesis.