MECHANISMS OF DIETARY FAT EFFECTS IN COLON CANCER

  • Suh, Nanjoo (PI)
  • Reddy, Bandaru (PI)
  • Reddy, Bandaru S. (PI)
  • Reddy, Bandaru (PI)
  • Reddy, Bandaru S. (PI)
  • Reddy, Bandaru S. (PI)
  • SUH, NANJOO (PI)

Project Details

Description

The long term objective of the proposed program is to elucidate the role of
types and levels of dietary fat in colon carcinogenesis. The specific aims
are: (1) to compare the dose-response effect of 5, 10, 12.5, 15 and 20%
corn oil or lard on the initiation and promotional stages of colon cancer;
(2) to determine the threshold level at which types of dietary fat exerts
measurable effects on colon cancer; (3) to assess the effect of types of
dietary fat during the initiation stage of colon carcinogenesis using
carcinogen metabolism and DNA methylation as indicators; (4) to assess the
effect of types of fat during the promotional stage using colonic secondary
bile aids and 7Alpha-dehydroxylase and colonic mucosal ornithine
decarboxylase (ODC) activity as indicators, and (5) to determine the effect
of types and levels of fat on prostaglandins and prostaglandin synthetase
activity of colon tumors. From these it is possible to determine the
mechanism by which the types of dietary fat affect the colon tumor
initiation and promotion.

At 35 days of age, groups of male F344 rats will be fed the diets
containing 5, 10, 12.5, 15 and 20% corn oil or lard (for initiation study)
or the diets containing 5% corn oil or lard (for promotion study) and
continued on these diets during and 3 days after carcinogen treatment. At
56 days of age, all animals except vehicle controls will receive a single
s.c. dose of azoxymethane (AOM) (20 mg/kg bw). Three days after AOM or
vehicle (normal saline) treatment, all groups of animals intended for
initiation study will be transferred to their respective 5% fat diets and
continued until the termination of the experiment, whereas the animals
intended for promotion study will be transferred to their respective 5% 10,
12.5, 15 and 20% corn oil or lard diets and continued on these diets until
the termination of the experiment, which is 32-34 weeks after AOM
injection. Some of the animals fed various diets and intended for
initiation study will be used for the determination of the activities of
hepatic and colonic mucosal enzymes involved in AOM metabolism and of
hepatic and colonic mucosal DNA methylation. Fecal bile acids, colonic
7Alpha-dehydroxylase and colonic mucosal ODC levels will be determined in
animals intended for promotion study. Prostaglandin and prostaglandin
synthetase activity will be determined in colon tumors.
StatusFinished
Effective start/end date12/31/894/30/09

Funding

  • National Cancer Institute: $275,408.00

ASJC

  • Public Health, Environmental and Occupational Health
  • Medicine(all)
  • Oncology
  • Cancer Research

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