Importance of diabetes in inhibition of pancreatic cancer by streptozotocin.
Previous studies in our laboratory have demonstrated that the beta-cell toxin streptozotocin (STZ) inhibits the development of exocrine pancreatic cancer in the hamster when STZ is administered prior to treatment with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). Because the administration of STZ leads to diabetes, we wished to determine whether the presence of diabetes was important in the inhibitory effect of STZ on pancreatic carcinogenesis or whether STZ acted through a mechanism unrelated to diabetes, perhaps by a direct toxic effect on tumor precursor cells. Whole pancreas transplantation was used to create a two-pancreas hamster model to test this hypothesis. The study demonstrated that (1) STZ inhibits the induction of pancreatic cancer in the hamster when given prior to BOP and (2) the inhibitory effect of STZ was demonstrable only when diabetes was present. The inhibitory effect of STZ appears to be systemic, related to diabetes, and not a direct effect on the pancreas.
Bell
R H
RH
Department of Surgery, Veterans Administration Medical Center, Cincinnati, Ohio.
Sayers
H J
HJ
Pour
P M
PM
Ray
M B
MB
McCullough
P J
PJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000209:etiology; D008647:Mesocricetus; D009602:Nitrosamines / Q000037:antagonists & inhibitors*; D016035:Pancreas Transplantation; D010190:Pancreatic Neoplasms / Q000097:blood / Q000139:chemically induced*; D011292:Premedication; D013311:Streptozocin / Q000494:pharmacology*
D001786:Blood Glucose; D002273:Carcinogens; D009602:Nitrosamines; D013311:Streptozocin; C013622:nitrosobis(2-oxopropyl)amine