Arachidonic Acid Metabolism and Tumor Promotion

Prostaglandins, Leukotrienes, and Cancer is a multi-volume series that will focus on an emerging area of cancer research. In 1968, R.H. Williams first reported that elevated prostaglandin levels are present in human medullary car cinoma. Since that time, the concept that arachidonic acid metabolites may be in volved 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 of bioactive lipids produced from unsaturated fatty acids (principally from and lipoxygenase pathways, respec arachidonic acid) via the cyclooxygenase tively. Cyclooxygenase products consist of diverse products such as prosta glandin E2 (POE), prostacyclin (POI) and thromboxane A2 (TXA), whereas 2 2 2 lipoxygenase products consist of hydroperoxy fatty acids and mono-, di- and tri-hydroxy acids including leukotrienes. 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 of the metabolism of pros taglandins indicated 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 or in the vicinity of target tissues leading to the concept that prostaglandins are local hormones or autocoids.

Inhalt

1. Arachidonic Acid Metabolism in the Skin.- 2. Arachidonic Acid Metabolism and Tumor Promotion.- 3. Prostaglandins, Epidermal Hyperplasia and Skin Tumor Promotion.- 4. Effects of Phorbol Esters on Phospholipid Metabolism in Vitro.- 5. Tumor Promoting Phorbol Esters May Affect Cell Membrane Signal Transmission by Protein Kinase.- 6. Active Oxygen and Promotion.- 7. Possible Involvement of Arachidonate Products in Tumor Promoter Inhibition of Cell-Cell Communication.- 8. Proteases and Cyclic Nucleotides.- Perspectives.