The long-term objective is to understand the modulating effect of types of dietary fat differing in fatty acid composition on colon cancer. Specifically, it is proposed to study the mechanism(s) of types and amount of fat namely corn oil (CO) and menhaden fish oil (FO) on colon carcinogenesis. Azoxymethane (AOM), an aliphatic azoxy compound will be used to induce colon tumors. The effect of types and amount of dietary fat on the relevant biochemical parameters that are associated with colon tumor promotion will be determined and will include cecal bacterial 7alpha-dehydroxylase and phospholipase C activities, fecal diglycerides and bile acids, and colonic mucosal and tumor, 1,2-diacylglycerol, phospholipase C, DAG kinase, protein kinase C, prostaglandin synthesis, arachidonic acid metabolism via cyclooxygenase pathway, and ras p21. At 5 weeks of age, male F344 rats will be fed low-fat AIN-76A diet. At 7 weeks of age, groups of rats will be treated with two weekly s.c. doses of AOM or normal saline (vehicle) and transferred to high fat diets containing CO or FO diet. Then, day at 1 and week 1 and 12 following AOM treatment and at termination (wk 42), the above biochemical parameters will be measured in colon mucosa and tumors (at termination) to elucidate the mechanistic role of types and amount in colon carcinogenesis. Also, during the weeks of 4 and 12 on experimental diets and at termination, groups of animals from each dietary group treated with AOM will be sacrificed and cecal bacterial 7alpha-dehydroxylase and phospholipase C and fecal bile acids and diglycerides will be determined. Biochemical and physiological parameters of various dietary groups will be analyzed statistically to determine the significance of difference. The selected biochemical parameters taken together would suggest the possible mechanism of in vivo tumor promotion or inhibition by types of dietary fat.
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