Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid
Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid
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DOI：
10.1093/carcin/20.6.1019
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发表时间：
1999-06-01
期刊：
影响因子：
4.7
通讯作者：
Ip, C
中科院分区：
文献类型：
--
作者：
Banni, S;Angioni, E;Ip, C
以往的研究表明，共轭亚油酸（CLA）喂养期间的青春期乳腺发育的大鼠导致乳腺上皮分支减少，这可能是降低乳腺癌的风险。末端芽（TEB）是啮齿动物乳腺癌化学诱导的主要部位。本研究的目的之一是通过增加膳食CLA水平来研究TEE密度的调制，并确定这可能如何影响甲基亚硝基脲诱导的乳腺癌发生的风险。数据显示0.5和1% CLA产生的TEE密度和乳腺肿瘤产率的分级和平行降低。当饲料中的CLA提高到1.5%或2%时，没有观察到任何参数的进一步降低。因此，青春期最佳的CLA营养可以控制乳腺中癌症敏感靶位点的数量。由于CLA和亚油酸可能共享相同的链去饱和和延长酶系统，因此增加CLA摄入量可能会干扰亚油酸的进一步代谢。总脂质的脂肪酸分析表明，CEA和CLA代谢物继续积累在乳腺组织中的剂量依赖性的方式超过0.5-2%的CLA的范围。在组织亚油酸中没有扰动，然而，亚油酸代谢物（包括18：3、20：3和20：4）一致地被高达1%的CLA抑制。特别感兴趣的是20：3（花生四烯酸）的显著下降，其是类花生酸生物合成的环氧合酶和脂氧合酶途径的底物。因此，CLA对花生四烯酸抑制的剂量-反应效应与CLA对乳腺癌保护的剂量-反应效应密切对应。这一信息是至关重要的，在提供新的见解有关的生化作用的共轭亚油酸。
Previous research suggested that conjugated linoleic acid (CLA) feeding during the period of pubescent mammary gland development in the rat resulted in diminished mammary epithelial branching which might account for the reduction in mammary cancer risk. Terminal end buds (TEB) are the primary sites for the chemical induction of mammary carcinomas in rodents. One of the objectives of the present study was to investigate the modulation of TEE density by increasing levels of dietary CLA and to determine how this might affect the risk of methylnitrosourea-induced mammary carcinogenesis. The data show a graded and parallel reduction in TEE density and mammary tumor yield produced by 0.5 and 1% CLA. No further decrease in either parameter was observed when CLA in the diet was raised to 1.5 or 2%. Thus, optimal CLA nutrition during pubescence could conceivably control the population of cancer-sensitive target sites in the mammary gland. Since both CLA and linoleic acid are likely to share the same enzyme system for chain desaturation and elongation, it is possible that increased CLA intake may interfere with the further metabolism of linoleic acid. Fatty acid analysis of total lipid showed that CEA and CLA metabolites continued to accumulate in mammary tissue in a dose-dependent manner over the range 0.5-2% CLA. There was no perturbation in tissue linoleic acid, however, linoleic acid metabolites (including 18:3, 20:3 and 20:4) were consistently depressed by up to 1% CLA, Of particular interest was the significant drop in 20:3 (arachidonic acid), which is the substrate for the cyclooxygenase and lipoxygenase pathways of eicosanoid biosynthesis, Thus the CLA dose-response effect on arachidonic acid suppression corresponded closely with the CLA dose-response effect on cancer protection in the mammary gland. This information is critical in providing new insights regarding the biochemical action of CLA.