Chemoprevention by amiloride of experimental carcinogenesis in rat colon induced by azoxymethane.
The effects of amiloride on the incidence and histology of colon tumors induced by azoxymethane, on the labeling index of the colon mucosa and on the activity of ornithine decarboxylase in the colon wall were investigated in Wistar rats. Rats received 10 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 form every other day for 35 weeks. Prolonged administration of amiloride at a dose of 7.5 mg/kg, but not 5 mg/kg, significantly reduced the incidence of colon tumors at week 35. However, administration of amiloride had little or no significant influence on the histological types of colon tumors and cancers. Administration of amiloride at 7.5 mg/kg significantly decreased the labeling index of the colon mucosa and ornithine decarboxylase activity in the colon wall during and after administration of azoxymethane. These findings suggest that amiloride inhibits development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by amiloride is its suppression of proliferation of colon tumor cells.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Center for Adult Diseases-Osaka, Japan.
Iishi
H
H
Baba
M
M
Uehara
H
H
Nakaizumi
A
A
D000584:Amiloride / Q000627:therapeutic use*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D016588:Anticarcinogenic Agents; D000584:Amiloride; D009955:Ornithine Decarboxylase; D001397:Azoxymethane