It has been well established by human epidemiological studies and laboratory animal investigations that quantitative differences in dietary fat can affect mammary tumor development. Recently, our laboratory has provided evidence that qualitative differences in the polyunsaturated fatty acid composition (omega-3 vs omega-6) of the dietary lipids also can significantly modify mammary tumor development. Both qualitative and quantitative dietary lipid modifications appear to mediate their effects during the post- initiation phase of tumor development and are greatly affected by the ambient hormone environment. The biochemical processes responsible for these dietary lipid effects on tumor development are poorly understood, but the data available indicate that diet induced alterations in tumor membrane lipids may be particularly important. It is hypothesized that such membrane alterations may affect tumor cell function and development by modifying the composition of the substrate lipid molecules available for post-receptor signal processing. Many polypeptide hormones and autocrine growth factors are known to initiate their actions on tumor cells through membrane receptors. The objective of this study is to test this hypothesis by searching for specific changes in eicosanoid metabolism and hormone responsiveness of mammary tumors from rats maintained on different lipid diets. Particular effort will be made to biochemically define the phospolipid and fatty acid changes in the membrane lipids induced by diets containing varying amounts of omega-3 polyunsaturated fatty acids and observing the """"""""in vivo"""""""" and """"""""in vitro"""""""" changes in eicosanoid metabolism associated with them. It is hoped that this information will help provide a rational scientific basis for future development of effective nutritional and/or pharmacological approaches to human breast cancer prevention and therapy.
Cave Jr, W T (1991) Dietary n-3 (omega-3) polyunsaturated fatty acid effects on animal tumorigenesis. FASEB J 5:2160-6 |
Cave Jr, W T (1991) Omega 3 fatty acid diet effects on tumorigenesis in experimental animals. World Rev Nutr Diet 66:462-76 |
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Hildreth, N G; Schneider, A B; Cave Jr, W T (1987) A comparative study between individuals receiving thymic irradiation in infancy and their nontreated siblings: clinical and laboratory thyroid abnormalities. Radiat Res 110:458-67 |
Jurkowski, J J; Cave Jr, W T (1985) Dietary effects of menhaden oil on the growth and membrane lipid composition of rat mammary tumors. J Natl Cancer Inst 74:1145-50 |