MODULATION OF TUMOR PROMOTION BY CONGATED DIENOIC LINOLEATE

本研究的总体目标是阐明可能的机制 肿瘤发生的饮食脂质调节。 这些研究结果 研究很重要，因为环境因素，包括饮食， 虽然在癌症的发展中起着重要的作用， 人类 在似乎调节肿瘤发生的饮食因素中， 膳食脂质的数量和质量已被广泛研究 在实验动物身上。 最近有报道称， 与肿瘤抑制相关的饮食亚油酸的量 12-O-十四酰基佛波醇-13-乙酸酯（TPA）在小鼠皮肤中的促进作用 启动-促进癌症模型。 这些发现不同于 在乳腺和胰腺中， 亚油酸与实验性肿瘤反应增加相关， 动物 在皮肤模型中的独特发现促使了进一步的研究。 研究亚麻酸衍生的共轭二烯 （共轭二烯亚油酸酯; CLA）对TPA皮肤肿瘤促进的作用。 这些 在动物组织中发现的亚麻酸衍生产品， 包括油炸碎牛肉和加工奶酪在内的食品 先前显示抑制小鼠皮肤中的肿瘤起始， 大鼠乳腺肿瘤发生。 为了调查可能的 通过CLA抑制肿瘤促进，本发明的总体方法 项目包括确定从亚油酸合成CLA的程度 并阐明了局部施用的 纯CLA对TPA启动子相关事件和小鼠肿瘤促进的影响 皮肤 将通过以下方式解决这些问题 问题：（1）局部应用CLA是否调节几种TPA启动子- 相关事件包括蛋白激酶C激活和分布， 鸟氨酸脱羧酶活性和血管通透性诱导 老鼠皮做的吗(2)局部应用CLA是否调节TPA肿瘤 在SENCAR小鼠皮肤中进行推广？(3)什么是内生的 小鼠皮肤、血浆和肝脏中的CLA含量？这些数据将 通过从这些器官中提取和分离脂质获得，然后 用气相色谱-质谱联用仪定量分析 分光光度法

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.