Carcinogenesis and Dietary Fat

Prostaglandins, Leukotrienes, and Cancer is a multi-volume series which focuses on an emerging area of cancer research. In 1968, R. H. Williams first reported that elevated prostaglandin levels are present in human medullary carcinoma. Since that time, the concept that arachidonic acid metabolites may be involved in cancer has expanded to include every aspect of the disease from cell transformation through metastasis. Prostaglandins and leukotrienes are generic terms used to describe a family ofbioactive lipids produced from unsaturated fatty acids (principally from arachidonic acid) via the cyclooxygenase and lipoxygenase pathways, respectively. Cyclooxygenase products consist of diverse products such as prostaglandin E2 (PGE2), prostacyclin (PGI2) and thromboxane A2 (TXA2), whereas lipoxygenase products consist ofhydroperoxy fatty acids and mono-, di-and tri-hydroxy acids including leukotrienes, lipoxins, and epoxides. The precursor fatty acids for the cyclooxygenase and lipoxygenase pathways are present in cellular phospholipids. This finding established an important control point in their biosynthesis --the release of substrate. This occurs in response to numerous stimuli that act at the cell surface. Dr. Bengt Samuelsson's extensive study ofthe metabolism of prostaglandins indicate that they are rapidly inactivated on a single pass through pulmonary circulation. Thus, they cannot act as circulating hormones and appear to be made on demand in the vicinity oftarget tissues leading to the concept that prostaglandins are local rrormones or autocoids. Altered production, qualitative and/or quantitative, of prostaglandins and leukotrienes has been implicated in the development of a number of disease states (e. g.

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These 25 contributions provide a critical review of the literature on the possible roles played by dietary fat in carcinogenesis and evidence for the involvement of eicosanoids in the process. In spite of the abundance of data in the literature of the field, few insights into the mechanisms through

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Dietary Formulation and Feeding Regimens.- 1. Dietary Design in Fat and Cancer Research.- 2. Nutritional Methodology in Dietary Fat and Cancer Research.- Effects of Dietary Fat on Eicosanoid Production in Normal Tissues.- 3. Effects of Dietary Fat on Eicosanoid Production in Normal Tissues.- 4. Eicosanoids, Their Dietary Precursors and Drugs that Modify their Production or Actions: Implications in Cancer.- Mammary Tumors.- 5. Differential Effects of Specific Types of Dietary Lipid on Mammary Tumor Development.- 6. Dietary Fatty Acids and Mammary Tumorigenesis.- 7. Enhancement of Mammary Tumorigenesis by Dietary Fat: An Endocrine and/or Calorie Mechanism?.- Pancreatic Tumors.- 8. Role of Dietary Fat in Experimental Pancreatic Carcinogenesis.- Colon Tumors.- 9. Etiology of Colon Cancer.- 10. Autoxidation Products and Intestinal Carcinogenesis.- Metastasis and Eicosanoids.- 11. Prostaglandins and Tumor Metastasis.- 12. Tumor Metastasis: The Possible Role of Eicosanoids.- 13. PGE2 Mediated Inactivation of Potentially Tumorcidal Effector Cells of the Host During Tumor Development: Relevance to Metastasis and Immunotherapy.- 14. Regulation of Tumor Cell Adhesion and Motility by Arachidonic Acid Metabolism.- Human Tumors.- 15. Polyunsaturated Fatty Acids and Human Cancer.- Tumor Cell Heterogeneity.- 16. Tumor Tissue Dynamics and Diet in Breast Cancer.- 17. Factors Involved in the Development and Maintenance of Tumor Heterogeneity.- Immunological Aspects.- 18. Polyunsaturated Fat-induced Immune Suppression: Involvement of Prostaglandin Producing Suppressor Cells.- 19. Tumor-Mediated Immunosubversion: Role of Dietary Essential Fatty Acids.- 20. Dietary Fat, Lipids, Immunology in Carcinogenesis.- 21. Mechanisms of Dietary Fat Involvement in Tumorigenesis: Role of Fatty Acidsand Eicosanoids in Macrophage Function.- Cell Separation and Identification.- 22. Cell Separation and Identification.- Cell Culture.- 23. Differential Responsiveness of Normal and Neoplastic Mammary Epithelium to Unsaturated vs. Saturated Fatty Acids.- 24. The Role of Fatty Acids in Murine and Human Mammary Carcinogenesis: An In Vitro Approach.- 25. Cell Culture Strategies for Analysis of Dietary Variables in Cancer.