High dietary fat, particularly saturated and unsaturated omega-6 fatty acid, have been associated with as increased incidence of colon cancer. The efficacy of fish oil, rich in omega-3 fatty acids, and given as a dietary supplement, has reduced or delayed the development of experimentally induced colon cancer (Reddy and Maruyama, Cancer Res. 46:3367-3370, 1986). This laboratory would extend this observation with the following experiments: 1) Develop a dose response curve to establish the ratio of omega-6 to omega-3 fatty acids which best inhibits methylaxocymethanol (MAM) induced colon tumors in Sprague Dawley rats, 2) determine the phase of carcinogenesis (initiation-promotion stages) at which fish oil is most effective, and 3) assess varying systems to suggest a mechanism of action for the test agent. The latter aim would include evaluation of prostaglandin levels in colonic tissue, determination of the influence of fish oil on the metabolism and damaging effect of the carcinogen, and, lastly, examination of the effect of omega-3 fatty acids on colonic epithelial cell proliferation in normal, preneoplastic, and neoplastic tissue. This study may provide evidence that a naturally occurring substance namely marine lipid with its high omega-3 fatty acid composition is useful as a chemopreventive substance for individuals at high risk for colon cancer and that, additionally, the agent is important to balance the high consumption of polyunsaturated and saturated (omega-6) fatty acids found in Western diets.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046845-03
Application #
3190305
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1988-02-08
Project End
1991-12-31
Budget Start
1990-02-01
Budget End
1991-12-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Deschner, E E; Ruperto, J F; Wong, G Y et al. (1993) The effect of dietary quercetin and rutin on AOM-induced acute colonic epithelial abnormalities in mice fed a high-fat diet. Nutr Cancer 20:199-204
Huang, M T; Deschner, E E; Newmark, H L et al. (1992) Effect of dietary curcumin and ascorbyl palmitate on azoxymethanol-induced colonic epithelial cell proliferation and focal areas of dysplasia. Cancer Lett 64:117-21
Lytle, J S; Lytle, T F; Newmark, H L et al. (1992) Stability of a commercially prepared fish oil (omega-3 fatty acid) laboratory rodent diet. Nutr Cancer 17:187-94
Deschner, E E; Ruperto, J; Wong, G et al. (1991) Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis 12:1193-6
Deschner, E E; Ruperto, J F; Lupton, J R et al. (1990) Dietary butyrate (tributyrin) does not enhance AOM-induced colon tumorigenesis. Cancer Lett 52:79-82
Deschner, E E; Lytle, J S; Wong, G et al. (1990) The effect of dietary omega-3 fatty acids (fish oil) on azoxymethanol-induced focal areas of dysplasia and colon tumor incidence. Cancer 66:2350-6
Kerr, L D; Olashaw, N E; Matrisian, L M (1988) Transforming growth factor beta 1 and cAMP inhibit transcription of epidermal growth factor- and oncogene-induced transin RNA. J Biol Chem 263:16999-7005