Inhibition by amiloride of experimental carcinogenesis induced by azaserine in rat pancreas.
The effects of prolonged administration of the diuretic amiloride on pancreatic carcinogenesis induced by azaserine and on the labeling index of carcinogen-induced pancreatic lesions were investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight azaserine and also 5 mg/kg body weight amiloride every other day until the end of the experiment at week 62. Carcinogen-induced pancreatic lesions were examined by histochemical techniques and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histologic analysis showed that prolonged administration of amiloride significantly reduced the number and size (as percent of parenchyma) of ATPase-positive pancreatic lesions, which are closely correlated with the subsequent 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 pancreatic lesions. These findings indicate that amiloride inhibits pancreatic carcinogenesis, and that this effect may be related to the reduction of ATPase-positive lesions and to amiloride's inhibition of cell proliferation in neoplastic lesions of the pancreas.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Iishi
H
H
Baba
M
M
Yano
H
H
Iseki
K
K
Uehara
H
H
Nakaizumi
A
A
D000251:Adenosine Triphosphatases / Q000032:analysis; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001377:Azaserine / Q000633:toxicity*; D014408:Biomarkers, Tumor / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D008297:Male; D008940:Mitotic Index / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D002273:Carcinogens; D000584:Amiloride; D001377:Azaserine; D000251:Adenosine Triphosphatases