Eicosanoid Synthesis in Mammary Tumors of Rats Fed Varying Types and Levels of N-3 and/or N-6 Fatty Acids

Abstract

In previous studies (1,2), we have shown that the incidences of dimethylbenzanthracene (DMBA)-induced mammary tumors are decreased in animals fed diets containing the n-6 fatty acid, gammalinolenic acid (GLA) as contained in primrose oil (PO); and the n-3 fatty acids contained in menhaden oil (MO). Synthesis of eicosanoids was decreased in mammary fat pads of control rats and in mammary tumors of DMBA-treated rats by feeding high fat diets containing the n-3 fatty acids. Feeding a GLA source increased the ratio of monoenoic to dienoic eicosanoids compared to feeding either 20% corn oil (CO) or MO diets (2). In a study designed to explore mechanism(s) by which n-3 and/or n-6 polyunsaturated fatty acids (PUFAs) inhibit or promote mammary tumorigenesis, difluoromethylornithine (DFMO) and/or indomethacin were given during mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets (3). This study demonstrated that diets containing high n-6 fatty acids enhance synthesis of cyclooxygenase, lipoxygenase, and ornithine decarboxylase (ODC) in mammary tumors. However, promotion of tumorigenesis by a 20% corn oil diet was not inhibited by blocking cyclooxygenase and/or ODC activities without significantly blocking 5-lipoxygenase. The combination of DFMO with a diet containing an n-3/n-6 fatty acid ratio of 1.2 profoundly inhibited (72%) tumor promotion. This study demonstrated that simultaneous inhibition of the arachidonic acid cascade (both cyclooxygenase and lipoxygenase) as well as polyamine synthesis may be necessary to achieve the greatest inhibition of tumorigenesis. The present study was designed to determine the optimal levels of n-3 fatty acids and/or GLA needed in a 20% fat diet to significantly inhibit mammary tumor promotion.