Epithelial cell hyperproliferation induced in the exocrine pancreas of mice by a Western-style diet Journal Article


Authors: Xue, L.; Yang, K.; Newmark, H.; Leung, D.; Lipkin, M.
Article Title: Epithelial cell hyperproliferation induced in the exocrine pancreas of mice by a Western-style diet
Abstract: Background: Pancreatic cancer is a common cause of mortality in the United States, with an estimated 27 800 people dying of the disease in this country in 1996. Epidemiologic studies have suggested that Western diets containing high fat, high protein, and low calcium contents are associated with increased incidence of pancreatic cancer. Purpose: We investigated whether a Western-style diet containing increased fat content and decreased calcium and vitamin D contents would induce epithelial cell hyperproliferation (excess cell duplication) or hyperplasia (excess cell accumulation) in the pancreas, as was previously demonstrated in the colon and mammary gland. Methods: C57BL/6J mice at 4 weeks of age were randomly assigned to one of two groups of 14 mice each. One group received the control diet ad libitum, and the other group was given the Western-style diet ad libitum. After 6, 9, and 15 weeks on the diet, four or five mice per group were infused with 5-bromo-2'-deoxyuridine (BrdU) for 72 hours by use of subcutaneously implanted Alzet osmotic pumps. The mice were then killed, and the pancreas of each mouse was removed. In the exocrine pancreas with ductal secretion, the duct system (including interlobular and intralobular ducts and centroacinar [i.e., centroductular] cells) and acini were measured both histopathologically and immunohistochemically (BrdU) and were analyzed without knowledge of the source of the specimens. Two-way analysis of variance was carried out. All P values were generated from two-sided tests for statistical significance. Results: The number of pancreatic ducts (interlobular, intralobular, and centroacinar-cancer-prone regions in certain rodent models and in humans) and acini per mouse in the Western-style diet group was similar to that in the control diet group during the entire feeding period (P = .76, .32, .93, and .42, respectively). Statistically significant higher BrdU-labeling indices of the ductal interlobular and intralobular epithelial cells were seen in mice fed the Western-style diet than in mice fed the control diet during the entire observation period (P = .014 and .016, respectively). There was no statistically significant difference (P = .098) between both diet groups in the BrdU-labeling indices of the centroacinar epithelial cells. Conclusions: A Western-style diet induced pancreatic epithelial cell hyperproliferation in mice, further suggesting that increased fat content and decreased calcium and vitamin D contribute to the development of pancreatic neoplasms.
Keywords: immunohistochemistry; controlled study; nonhuman; pancreas cancer; pancreatic neoplasms; pancreas; cell proliferation; mouse; animals; mice; cell division; animal experiment; animal model; cancer research; mice, inbred c57bl; carcinogenesis; diet; vitamin d; hyperplasia; epithelium; morphometrics; random allocation; dietary fats; article; calcium, dietary
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 88
Issue: 21
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 1996-11-06
Start Page: 1586
End Page: 1590
Language: English
DOI: 10.1093/jnci/88.21.1586
PUBMED: 8901857
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Denis Heng Yan Leung
    114 Leung
  2. Martin   Lipkin
    116 Lipkin
  3. Harold L. Newmark
    61 Newmark
  4. Kan Yang
    24 Yang