ABSTRACT
It has been reported that there is an association between pancreatic cancer and obesity, impaired glucose metabolism and diabetes based on excess dietary fat and sugar intakes. A number of studies have suggested that a high-fat diet increases development of carcinomas in various organs and possible risk factors for pancreatic cancer. However, how an excess sugar intake promotes pancreatic carcinogenesis is still unknown. In the present study, we investigated the influence of an excess sugar intake on pancreatic carcinogenesis by administration of a sucrose-rich diet in which starch was replaced by sucrose in order to contain the same calories and other nutrients. Two similar experiments were performed. Six-week-old male Syrian golden hamsters were given N-nitrosobis (2-oxopropyl) amine (BOP) at a dose of 50 and 20 mg/kg body weight as a carcinogen in Week 0 and 1, respectively. In Week 2, the animals were divided into control and experimental groups. In experiment 1, 15 animals received a control diet or sucrose-rich diet in which 100% of the starch was replaced by sucrose, respectively. Since five animals fed on the sucrose-rich diet died by Week 12, the diet was changed to a sucrose-rich diet in which 50% of the starch was replaced by sucrose. In experiment 2, 15 animals received a control diet or sucrose-rich diet in which 50 or 20% of the starch was replaced by sucrose, respectively. All animals were sacrificed 25 weeks after the start of the experiment, and histological examination of the pancreas was performed. No significant difference was seen in the body weight at the end of the experiment. There were no significant differences in the glycosylated hemoglobin (HbA1c) and serum triglyceride, total cholesterol and HDL-cholesterol levels between the control and sucrose-rich diet groups in experiments 1 and 2. The incidence and number of carcinomas increased in hamsters fed the sucrose-rich diet compared with the control diet in experiments 1 and 2. These results suggest that an excess sucrose intake may promote the development of pancreatic cancer in hamsters.
ABSTRACT
Changes in p53 expression, apoptosis and cell proliferation after treatment with 4-hydroxyaminoquinoline 1-oxide (4HAQO) were investigated in the rat pancreas and liver, target and nontarget organs for tumorigenesis, respectively. Male rats were given a single intravenous injection of 4HAQO at a dose of 20 mg/kg body weight and control rats received vehicle alone and were euthanized after 2-72 hours. Pancreata and livers were removed for histopathological examination, immunohistochemistry for p53 protein, PCNA and Ki-67, and TUNEL labeling and electron microscopic observation for detecting apoptosis. In the pancreas, p53 expression and apoptosis were significantly increased first at 4 and 6 hours, respectively, while no change was evident in the liver. The rates peaked at 24 hours, consistent with the peak for PCNA-labeling, while Ki-67-labeling rates peaked at 72 hours. Electron microscopically, apoptotic changes in pancreatic acinar cells were observed after 2 hours. No significant apoptosis, p53 expression or cell proliferation were noted in the pancreatic tissues of the control rats nor in liver cells regardless of 4HAQO treatment. Taken together with our previous data, the results suggest that apoptosis, p53 expression, and enhanced cell replication are closely related phenomena involved in the carcinogenesis of 4HAQO following DNA adduct formation.
