Inhibition of initiation and promotion by N-methylnitrosourea-induced colon carcinogenesis in rats by non-steroid anti-inflammatory agent indomethacin.

The non-steroid anti-inflammatory drug indomethacin, a prostaglandin synthesis inhibitor, may play a role to prevent the chemically induced colon cancer development in rats. CD-Fischer rats were given 3 intrarectal doses of 4 mg N-methyl-N-nitrosourea in week 1 as an initiation procedure to induce colon cancer. The experimental groups received a 0.001% water solution of indomethacin freely as drinking water at various times either during the initiation stage or the subsequent promotion stage. At autopsy in week 31, the treatment reduced the colon cancer development in the group of rats treated for week 1 (initiation stage), and for week 2-30 (early and late promotion stages) and for week 11-30 (late promotion stage), compared with untreated controls. However, removal of the treatment after effective treatment in promotion stage permitted the cancer development, and it suggests that the initiated cells are surviving during the treatment in promotion stage. It is concluded that indomethacin may inhibit methylnitrosourea-induced initiation and regulate promotion in colon carcinogenesis, presumably correlated with an inhibition of prostaglandin synthesis in the colon by indomethacin.