Modulation of Tumor Promotion by Congated Dienoic Linoleate

Belury, Martha

Abstract

The overall objective of this study is to elucidate possible mechanisms of dietary lipid modulation of tumorigenesis. The findings from these studies are important since environmental factors, including diet, are though to contribute significantly to the development of many cancers in humans. Among dietary factors which appear to modulate tumorigenesis, the quantity and quality of dietary lipids has been studied extensively in experimental animals. Recently, it was reported that increasing amounts of dietary linoleate correlated with inhibition of tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the mouse skin initiation-promotion cancer model. These findings were unlike findings in the mammary gland and pancreas where increasing amounts of dietary linoleate has correlated with increased tumor responses in experimental animals. The unique findings in the skin model prompted a further set of studies investigating the role of linoleate-derived conjugated dienes (conjugated dienoic linoleate; CLA) on TPA skin tumor promotion. These linoleate-derived products which have been found in animal tissues and food products including fried ground beef and processed cheeses have previously been shown to inhibit tumor initiation in mouse skin nd tumorigenesis in rat mammary gland. In order to investigate the possible inhibition of tumor promotion by CLA, the overall approach of this project includes determining the extent of CLA synthesis from linoleate in the mouse and elucidating the modulatory role of topically applied pure CLA on TPA promoter-associated events and tumor promotion in mouse skin. These approachers will be addressed through the following questions: (1) Does topically applied CLA modulate several TPA promoter- associated events including protein kinase C activation and distribution, induction of ornithine decarboxylase activity and vascular permeability in mouse skin? (2) Does topically applied CLA modulate TPA tumor promotion in SENCAR mouse skin? (3) What is the endogenously produced amount of CLA in mouse skin, plasma, and liver? These data will be obtained by extracting and separating lipids from these organs, then quantifying them with the use of gas chromatography-mass spectrophotometry.