Modulation of phorbol ester skin tumor promotion in mice by dietary fatty acids

Many cancers in experimental animals have been shown to be modulated by different types of saturated and polyunsaturated dietary fats. In particular, a correlation between increased levels of dietary n-6 polyunsaturated fatty acids and increased tumor incidence and/or yield has been observed. In contrast, animals fed diets high in n-3-rich polyunsaturated fats have exhibited reduced tumorigenesis. In the present studies the effects of specific dietary polyunsaturated fatty acids on 12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin tumor promotion were assessed using three approaches. First, using cultured mouse epidermal cells in a serum-free in vitro system, cultures supplemented with either linoleate (LA; 18:2n-6), arachidonate (AA; 20:4n-6) or eicosapentaenoate (EPA; 20:5n-3) responded differently to TPA treatment. Compared to cultures supplemented with AA, cultures containing LA and EPA did not support as great a response to TPA-induced prostaglandin (PG) E...