Chemoprevention by amiloride of experimental carcinogenesis in rat colon induced by azoxymethane

The effects of amiloride on the incidence and histology of colontumors induced by azoxymethane, on the labeling index of thecolon mucosa and on the activity of ornithine decarboxylasein the colon wall were investigated in Wistar rats. Rats received10 weekly injections of 7.4 mg/kg body wt azoxymethane and s.c.injections of 5 or 7.5 mg/kg body wt amiloride in depot formevery other day for 35 weeks. Prolonged administration of amilorideat a dose of 7.5 mg/kg, but not 5 mg/kg, significantly reducedthe incidence of colon tumors at week 35. However, administrationof amiloride had little or no significant influence on the histologicaltypes of colon tumors and cancers. Administration of amilorideat 7.5 mg/kg significantly decreased the labeling index of thecolon mucosa and ornithine decarboxylase activity in the colonwall during and after administration of azoxymethane. Thesefindings suggest that amiloride inhibits development of colontumors. A possible mechanism of inhibition of colon carcinogenesisby amiloride is its suppression of proliferation of colon tumorcells.