MODULATION OF TUMOR PROMOTION BY CONGATED DIENOIC LINOLEATE

这项研究的总体目标是阐明可能的机制。 膳食脂肪对肿瘤发生的调节作用。这些研究的结果 研究很重要，因为环境因素，包括饮食，是 虽然对许多癌症的发展有重大贡献 人类。在似乎调节肿瘤发生的饮食因素中， 膳食脂肪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，越来越多的人 饮食中的亚油酸量与抑制肿瘤有关 12-O-十四酰佛波醇-13-乙酸酯(TPA)对小鼠皮肤的促进作用 启动促进型癌症模型。这些发现与其他发现不同 在乳腺和胰腺中，增加饮食的量 亚油酸盐与实验性肿瘤反应增加有关 动物。皮肤模型中的独特发现促使了另一组 研究亚油酸衍生的共轭双烯的作用 (共轭二烯亚油酸酯；共轭亚油酸)对TPA皮肤肿瘤的促进作用。这些 亚油酸衍生产品已在动物组织和 包括炸碎牛肉和加工奶酪在内的食品 先前被证明可以抑制小鼠皮肤和皮肤肿瘤的发生。 大鼠乳腺肿瘤的发生。为了调查可能发生的 共轭亚油酸抑制促癌作用的总体思路 项目包括确定从亚油酸酯合成共轭亚油酸的程度 并阐明局部应用的调节作用 纯共轭亚油酸对小鼠TPA启动子相关事件及促癌作用的研究 皮肤。我们将通过以下途径解决这些问题 问题：(1)局部应用CLA是否调节几个TPA启动子- 相关事件包括蛋白激酶C的激活和分布， 鸟氨酸脱羧酶活性和血管通透性的诱导 在小鼠皮肤上？(2)局部应用共轭亚油酸是否调节TPA肿瘤 在Sencar小鼠皮肤中的促进作用？(3)内源性产生的 小鼠皮肤、血浆和肝脏中的共轭亚油酸含量？这些数据将是 通过从这些器官中提取和分离脂类而获得，然后 用气相色谱-质谱法对它们进行定量 分光光度测定法。

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.