MODULATING EFFECT OF AMOUNT AND TYPES OF DIETARY-FAT ON ORNITHINE DECARBOXYLASE, TYROSINE PROTEIN-KINASE AND PROSTAGLANDINS PRODUCTION DURING COLON CARCINOGENESIS IN MALE F344 RATS

Epidemiological and laboratory animal model studies suggest that the effect of dietary fat on colon carcinogenesis depends on the amount and its type. In the present study, we investigated the modulating effect of high-fat diets rich in omega-3, omega-6 and omega-9 fatty acids on liver, colon and small intestine mucosal ornithine decarboxylase (ODC) and tyrosine-specific protein kinase (TPK) activities and plasma, liver and colon mucosal prostaglandin E2 (PGE2) and 6-keto prostaglandin F1alpha (6-keto PGF1alpha) levels in male F344 rats. At 6 weeks of age, groups of animals were fed the low-fat diet containing 5% corn oil (LFCO), or high-fat diets containing 23.5% corn oil (HFCO), 23.5% olive oil (HFOO) and 20.5% fish oil + 3% corn oil (HFFO). Two weeks later, all animals except the vehicle-treated groups received azoxymethane (AOM) s.c. once weekly for 2 weeks at a dose rate of 15 mg/kg body wt. All animals were killed 5 days later and liver, colon and small intestine mucosa were analyzed for ODC, TPK and PGs and plasma for PGs. Carcinogen treatment enhanced the ODC and TPK activities (P < 0.0001) in the liver and colon of animals, irrespective of dietary treatment. Dietary HFCO compared with LFCO significantly increased the ODC (P < 0.01) and membrane TPK (P < 0.05) activities in the liver and colon of carcinogen-treated animals, whereas the HFOO and HFFO diets significantly (P < 0.002) suppressed the ODC and membrane TPK (P < 0.05) activities in the liver and colon mucosa compared with the HFCO diet. Carcinogen treatment also significantly (P < 0.01) increased the PG levels in plasma, liver and colon. Feeding of the HFFO diet significantly suppressed both the basal levels and ex vivo production of PGE2 and 6-keto PGF1alpha levels compared with the HFCO diet, whereas the HFOO diet only decreased PGE2 in liver and colon. These results thus demonstrate that high levels of corn oil in the diet increase colon and liver ODC, TPK and PGs whereas high dietary levels of fish oil and olive oil suppress these activities.