Ip C, Chin S F, Scimeca J A, Pariza M W
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Cancer Res. 1991 Nov 15;51(22):6118-24.
Conjugated dienoic derivative of linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is a naturally occurring substance in food and is present at higher concentrations in products from animal sources. The present study reports that synthetically prepared CLA is an effective agent in inhibiting the development of mammary tumors induced by dimethylbenz(a)anthracene. Rats were fed either the AIN-76A basal diet or the same diet supplemented with 0.5, 1, or 1.5% CLA by weight. These diets were started 2 weeks before carcinogen administration and continued until the end of the experiment. The total number of mammary adenocarcinomas in the 0.5, 1, and 1.5% CLA groups was reduced by 32, 56, and 60%, respectively. The final tumor incidence and cumulative tumor weight were similarly diminished in rats fed the CLA-containing diets. In general, there appeared to be a dose-dependent protection at levels of 1% CLA and below, but no further beneficial effect was evident at levels above 1%. Chronic feeding of up to 1.5% CLA produced no adverse consequences in the animals. Analysis of the phospholipid fraction from liver and mammary tumor extracts showed that only the c9,t11 isomer of CLA was incorporated and that the level of incorporation increased with dietary intake. An interesting property of CLA is its ability to suppress peroxide formation from unsaturated fatty acid in a test-tube model (Cancer Res., Ha et al. 50: 1097-1101, 1990). In view of this information, the amount of thiobarbituric acid-reactive substances (lipid peroxidation products) present endogenously in liver and mammary gland was quantitated. The feeding of CLA (for either 1 or 6 months) resulted in a decrease in the extent of lipid peroxidation in the mammary gland, but such a suppressive effect was not detected in the liver. It should be noted that maximal antioxidant activity was observed with only 0.25% CLA in the diet, whereas maximal tumor inhibition was achieved at about 1% CLA. Hence there is a discrepancy between the antioxidant efficacy of CLA and its anticarcinogenic potency, suggesting that some other mechanisms might be involved in cancer protection. Unlike the stimulatory effect of linoleic acid in carcinogenesis (Cancer Res., Ip et al., 45: 1997-2001, 1985), the reaction of CLA in cancer prevention is specific, and CLA is more powerful than any other fatty acid in modulating tumor development.
共轭亚油酸（CLA）是亚油酸的共轭二烯衍生物的统称，它指的是亚油酸位置和几何异构体的混合物。它是食物中的天然物质，在动物源性产品中含量更高。本研究报告称，合成制备的CLA是抑制二甲基苯并（a）蒽诱导的乳腺肿瘤发生的有效试剂。给大鼠喂食AIN - 76A基础饮食或添加了0.5%、1%或1.5%（重量）CLA的相同饮食。这些饮食在给予致癌物前2周开始，持续到实验结束。在0.5%、1%和1.5%CLA组中，乳腺腺癌的总数分别减少了32%、56%和60%。喂食含CLA饮食的大鼠的最终肿瘤发生率和累积肿瘤重量也同样降低。一般来说，在CLA水平为1%及以下时似乎存在剂量依赖性保护作用，但在高于1%的水平时没有进一步的有益效果。长期喂食高达1.5%的CLA对动物没有产生不良后果。对肝脏和乳腺肿瘤提取物的磷脂部分分析表明，只有CLA的c9,t11异构体被纳入，且纳入水平随饮食摄入量增加。CLA的一个有趣特性是其在试管模型中抑制不饱和脂肪酸过氧化物形成的能力（《癌症研究》，哈等人，50: 1097 - 1101，1990）。鉴于此信息，对肝脏和乳腺中内源性存在的硫代巴比妥酸反应性物质（脂质过氧化产物）的量进行了定量。喂食CLA（1个月或6个月）导致乳腺中脂质过氧化程度降低，但在肝脏中未检测到这种抑制作用。应该注意的是，在饮食中仅含0.25%CLA时观察到最大抗氧化活性，而在CLA约为1%时实现最大肿瘤抑制。因此，CLA的抗氧化功效与其抗癌效力之间存在差异，这表明可能有其他机制参与癌症保护。与亚油酸在致癌作用中的刺激作用不同（《癌症研究》，伊普等人，45: 1997 - 2001，1985），CLA在癌症预防中的反应是特异性的，并且CLA在调节肿瘤发生方面比任何其他脂肪酸都更有效。
