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.
