Lock Adam L, Corl Benjamin A, Barbano David M, Bauman Dale E, Ip Clement
Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
J Nutr. 2004 Oct;134(10):2698-704. doi: 10.1093/jn/134.10.2698.
The present study was designed to determine whether the ability of vaccenic acid (trans-11 18:1; VA) to reduce the risk of chemically induced mammary carcinogenesis in rats is direct or is mediated via conversion to cis-9, trans-11 conjugated linoleic acid (CLA). We previously reported that dietary VA caused a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in the risk of mammary tumorigenesis. Specifically, our objective was to determine whether inhibiting Delta9-desaturase with cyclopropenoic fatty acids, supplied by sterculic oil (SO), would reverse the cancer-protective effect observed with a dietary supplement of VA-enriched butter. Female Sprague-Dawley rats were injected with a single dose of carcinogen (methylnitrosourea) and were fed 1 of 4 diets: 1) low VA (0.13% of diet), 2) low VA + SO (0.4% of diet), 3) high VA (1.60% of diet), and 4) high VA + SO. After 6 wk, the mammary glands were evaluated histologically for the appearance of premalignant lesions and were stained with bromodeoxyuridine to determine the extent of cell proliferation, and fatty acids were analyzed in plasma, liver, and mammary fat pad. The VA-enriched diet increased the tissue content of CLA, reduced the risk of developing premalignant lesions, and decreased the proliferative activity of premalignant cells in the mammary gland. Treatment with SO reversed the effects of VA. The anticarcinogenic effect of VA is predominantly, perhaps exclusively, mediated through its conversion to cis-9, trans-11 CLA via Delta9-desaturase, and when this conversion is blocked by SO, the biological response to VA is attenuated.
本研究旨在确定反式-11十八碳烯酸（VA）降低大鼠化学诱导性乳腺癌发生风险的能力是直接作用还是通过转化为顺-9，反-11共轭亚油酸（CLA）介导。我们之前报道过，日粮中的VA会导致乳腺脂肪垫中CLA的积累呈剂量依赖性增加，同时乳腺肿瘤发生风险也相应降低。具体而言，我们的目标是确定用来自苹婆油（SO）的环丙烯脂肪酸抑制Δ9-去饱和酶是否会逆转富含VA的黄油日粮所观察到的癌症预防效果。给雌性斯普拉格-道利大鼠注射单剂量致癌物（甲基亚硝基脲），并喂食4种日粮中的1种：1）低VA（日粮的0.13%），2）低VA+SO（日粮的0.4%），3）高VA（日粮的1.60%），4）高VA+SO。6周后，对乳腺进行组织学评估以观察癌前病变的出现情况，并用溴脱氧尿苷染色以确定细胞增殖程度，同时分析血浆、肝脏和乳腺脂肪垫中的脂肪酸。富含VA的日粮增加了CLA的组织含量，降低了癌前病变的发生风险，并降低了乳腺中癌前细胞的增殖活性。用SO处理可逆转VA的作用。VA的抗癌作用主要（可能是唯一）通过其经Δ9-去饱和酶转化为顺-9，反-11 CLA介导，当这种转化被SO阻断时，对VA的生物学反应就会减弱。
