title: Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model.
abstract: Previous studies have shown that some N-nitrosobis (2-oxopropyl)amine (BOP)-induced ductal/ductular pancreatic cancers in the hamster model develop within islets and that streptozotocin (SZ) pretreatment that caused islet degeneration and atrophy inhibits pancreatic cancer induction. Hence, it appears that in this model islets play a significant role in exocrine pancreatic carcinogenesis. To examine whether stimulation of islet cell proliferation (nesidioblastosis) enhances pancreatic exocrine cancer development, we tested the effect of the pancreatic carcinogen BOP in hamsters after induction of nesidioblastosis by cellophane wrapping. Before wrapping, hamsters were treated with SZ to inhibit pancreatic tumor induction in the unwrapped pancreatic tissues. Control groups with a wrapped pancreas did not receive SZ. Six weeks after SZ treatment, all hamsters were treated with BOP (10 mg/kg body weight) weekly for 10 weeks and the experiment was terminated 38 weeks after the last BOP treatment. Many animals recovered from their diabetes at the time when BOP was injected and many more after BOP treatment. Only nine hamsters remained diabetic until the end of the experiment. Both SZ-treated and control groups developed proliferative and malignant pancreatic ductal-type lesions primarily in the wrapped area (47%) but less frequently in the larger segments of the pancreas, including the splenic lobe (34%), gastric lobe (13%), and duodenal lobe (6%). Only a few lesions developed in the unwrapped pancreatic region of nine diabetic hamsters with atrophic islets, whereas seven of these hamsters had tumors in the wrapped area. Histologically, most tumors appeared to originate from islets, many invasive carcinomas had foci of islets, and some tumor cells showed reactivity with anti-insulin. The results show that, in the BOP hamster model, islets are the site of formation of the major fraction of exocrine pancreatic cancer and that induction of nesidioblastosis enhances pancreatic carcinogenesis.
authors.affiliation: UNMC/Eppley Cancer Center, University of Nebraska Medical Center, Omaha 68198-6805, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Pour
authors.forename: K
authors.initials: K
authors.lastname: Kazakoff
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002476:Cellophane; D006224:Cricetinae; D004195:Disease Models, Animal; D007279:Injections, Subcutaneous; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines; D010179:Pancreas / Q000473:pathology; D010183:Pancreatic Ducts / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D013311:Streptozocin / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: D000903:Antibiotics, Antineoplastic; D001786:Blood Glucose; D002273:Carcinogens; D009602:Nitrosamines; D013311:Streptozocin; C013622:nitrosobis(2-oxopropyl)amine; D002476:Cellophane