Abstract 2478: Early and enhanced development of N-nitrosobis(2-oxopropyl)amine-induced hamster pancreatic adenocarcinomas by high-fat diet

Abstract

Abstract Epidemiologically, obesity is associated with pancreatic cancer risk, but the mechanisms of obesity-associated carcinogenesis have not yet been clearly understood. Hypertrophic white adipose tissues secrete many adipokines and inflammatory factors, which are expected to enhance cancer development. Syrian golden hamsters, which are used in pancreatic carcinogenesis studies, are in a hyperlipidemic state even under normal diet conditions. We previously have shown that pioglitazone, a PPAR γ ligand, improves hyperlipidemia and suppresses N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic ductal carcinoma development. In the present study, effects of a high-fat diet (HFD) on hyperlipidemia and pancreatic carcinogenesis in BOP-treated hamsters were examined. Six-week-old female Syrian golden hamsters were subcutaneously injected with BOP (10 mg/kg body weight) four times in a week and from 8 weeks of age, the animals in the HFD groups were fed Quick Fat Diet (CLEA Japan, crude fat 14.3 %) for 6 or 17 weeks. At 14 weeks of age, serum levels of triglycerides, total cholesterol, free fatty acids and leptin were significantly elevated in hamsters fed the HFD, and pancreatic ductal adenocarcinomas were already observed in the BOP + HFD group. Pancreatic fatty infiltration was observed to increase in BOP-treated and HFD-fed hamsters. At 25 weeks of age, serum levels of total cholesterol and free fatty acids were further increased in each group and pancreatic ductal adenocarcinomas developed both in the BOP + standard diet group and BOP + HFD group. The numbers of dysplasia and adenocarcinomas in the pancreas were significantly higher in the BOP + HFD group than in the BOP + standard diet group. Apparent fatty infiltration was observed in relatively large adenocarcinomas in the BOP + HFD group. In conclusion, the HFD aggravated the hyperlipidemia, shortened the latency periods of cancer and increased numbers of BOP-induced pancreatic precancerous lesions and adenocarcinomas. Fatty infiltration was apparent in the pancreas of the HFD group and may be associated with pancreatic cancer development in hamsters. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2478.