INHIBITION BY AMILORIDE OF EXPERIMENTAL CARCINOGENESIS INDUCED BY AZASERINE IN RAT PANCREAS

The effects of prolonged administration of the diuretic amiloride on p ancreatic carcinogenesis induced by azaserine and on the labeling inde x of carcinogen-induced pancreatic lesions were investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight az aserine and also 5 mg/kg body weight amiloride every other day until t he end of the experiment at week 62. Carcinogen-induced pancreatic les ions were examined by histochemical techniques and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histologi c analysis showed that prolonged administration of amiloride significa ntly reduced the number and size (as percent of parenchyma) of ATPase- positive pancreatic lesions, which are closely correlated with the sub sequent development of pancreatic cancer. Amiloride also significantly decreased the labeling index of carcinogen-induced pancreatic lesions , but not of the surrounding acinar cells. In contrast, amiloride has no significant influence on the number and size of ATPase-negative pan creatic lesions. These findings indicate that amiloride inhibits pancr eatic carcinogenesis, and that this effect may be related to the reduc tion of ATPase-positive lesions and to amiloride's inhibition of cell proliferation in neoplastic lesions of the pancreas.