title: Inhibition by amiloride of experimental carcinogenesis induced by azaserine in rat pancreas.
abstract: 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.
authors.affiliation: Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tatsuta
authors.forename: H
authors.initials: H
authors.lastname: Iishi
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: H
authors.initials: H
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Iseki
authors.forename: H
authors.initials: H
authors.lastname: Uehara
authors.forename: A
authors.initials: A
authors.lastname: Nakaizumi
mesh_terms: 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
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D002273:Carcinogens; D000584:Amiloride; D001377:Azaserine; D000251:Adenosine Triphosphatases