It is well documented that cyclopropenoid fatty acids (CPFA) included in diets with various mycotoxins or other carcinogens greatly enhance the induction of liver cell cancer in rainbow trout. The mechanisms for this cocarcinogenic action remains unexplained. The basic objective of this project is to examine the effects of CPFA on the rate of protein synthesis and protein degradation, and to gain a better understanding of the interaction of CPFA with cellular membrane proteins involved with structural and catalytic activities. The effects of CPFA on the rates of protein synthesis and protein degradation will be studied using polyacrylamide gel electrophoresis and dual labeling techniques. The effect of CPFA on DNA repair will be assessed using autoradiographic techniques. The interaction of CPFA with membrane proteins through acylation of protein hydroxyl groups will be studied using 14C labeled sterculic acid as the acylating agent. The extent to which membrane proteins are acylated will be quantitated using various chromatographic techniques. These studies should provide information regarding the potential for membrane destabilization induced by CPFA. The effect of phospholipids containing CPFA on catalytic activity, cytochrome P-450 and the reductive enzymes will be determined in reconstituted enzyme systems and lipid vesicles by analyzing metabolite profiles of aflatoxin B1. The knowledge obtained from these studies will provide information to the specific nature of CPFA as a cocarcinogen, particularly the possibility that CPFA reduces important functional proteins. Moreover, the information obtained will provide new insights to our general understanding of cocarcinogenic mechanisms.
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