DIETARY-LIPID AND IRON MODIFY NORMAL COLONIC MUCOSA WITHOUT AFFECTING PHOSPHOLIPASE A(2) ACTIVITY

Phospholipase A(2) (PLA(2)) functions as the rare-limiting step in arachidonic acid metabolism and in the removal of damaged or peroxidized membrane lipids. It is elevated in some human tumors and may be involved with mechanisms of tumor promotion. In vitro systems have shown PLA(2) activity to be altered by variations in fatty acid and antioxidant components. This study encompassed two objectives. First, PLA(2) activity in colon tumors produced using azoxymethane (AOM) in Fischer-344 rats was examined. Secondly, this study tested the effect of iron supplementation as a potential pro-oxidant in diets of varied fatty acid composition on PLA(2) activity, Diets included 35 or 140 mg/kg of iron in AIN-76A-based diets high in corn oil, menhaden oil, or beef tallow. Results for the first objective showed PLA(2) activity to be significantly higher in colon tumors than in normal mucosa with the increase due primarily to an increase in activity within a particulate subcellular fraction. In the second objective, fatty acid composition of colon mucosa was altered by both dietary fat and iron. Animals fed beef tallow had the highest level of oleic acid and corn oil-fed animals had the highest level of linoleic acid. Animals fed menhaden oil had the lowest level of arachidonic acid and highest level of a-linolenic, eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids. Iron supplementation in diets high in corn oil resulted in decreased membrane composition of palmitoleic and delta-linolenic acid. In spite of these changes in membrane composition, there were no changes in PLA(2) activity. These results show that PLA(2) activity is increased in AOM-induced tumors but that diet alone does not influence PLA(2) activity in this model.