Sauer L A, Dauchy R T
Cancer Research Laboratory, Mary Imogene Bassett Hospital, Cooperstown, New York 13326.
Br J Cancer. 1992 Aug;66(2):297-303. doi: 10.1038/bjc.1992.260.
Ingestion of diets containing corn oil or marine fish oils is known to increase or decrease, respectively, the growth of transplantable rodent tumours. The active agents in these oils have been identified as linoleic acid (in corn oil) and omega-3 fatty acids (in marine oils), but it is still not known how they influence the tumour growth processes. In these experiments we examined the effects of plasma free omega-6 and omega-3 fatty acids on the rate of 3H-thymidine incorporation in tissue-isolated hepatoma 7288CTC perfused in situ. Host Buffalo rats were fed an essential fatty acid-deficient diet. Plasma and tumours in these animals contained low endogenous levels of both omega-6 and omega-3 fatty acids. Perfusion of these tumours for 2 h with donor whole blood containing added omega-6 free fatty acids, including 0.5 mM linoleic (C18:2,N-6), gamma-linolenic (C18:3,N-6), dihomo-gamma-linolenic (C20:3,N-6) or arachidonic acids (C20:4,N-6), increased the rate of 3H-thymidine incorporation. Linoleic acid was about three times more effective than the other omega-6 fatty acids. Typical hyperbolic substrate-saturation curves were observed as the plasma free linoleate or arachidonate concentration was increased. When perfused alone plasma free omega-3 fatty acids had no effect on tumour 3H-thymidine incorporation, but in the presence of linoleic acid the omega-3 fatty acids, alpha-linolenic (C18:3,N-3) and eicosapentaenoic (C20:5,N-3), competitively inhibited both tumour linoleate uptake and the stimulative effect on 3H-thymidine incorporation. The results suggest that the ambient plasma free linoleic and arachidonic acid concentrations in host arterial blood directly influence the rate of tumour DNA synthesis. Plasma free omega-3 fatty acids appear to modulate the effect of linoleic acid by competitively inhibiting its uptake. These relationships could explain the actions of dietary linoleic and omega-3 fatty acids on tumour growth in vivo.
已知摄入含有玉米油或鱼油的饮食会分别增加或减少可移植啮齿动物肿瘤的生长。这些油中的活性剂已被确定为亚油酸（玉米油中）和ω-3脂肪酸（鱼油中），但它们如何影响肿瘤生长过程仍不清楚。在这些实验中，我们研究了血浆游离ω-6和ω-3脂肪酸对原位灌注的组织分离肝癌7288CTC中3H-胸腺嘧啶核苷掺入率的影响。给宿主布法罗大鼠喂食必需脂肪酸缺乏的饮食。这些动物的血浆和肿瘤中内源性ω-6和ω-3脂肪酸水平都很低。用添加了游离ω-6脂肪酸的供体全血灌注这些肿瘤2小时，这些游离ω-6脂肪酸包括0.5 mM亚油酸（C18:2，N-6）、γ-亚麻酸（C18:3，N-6）、二高-γ-亚麻酸（C20:3，N-6）或花生四烯酸（C20:4，N-6），可提高3H-胸腺嘧啶核苷的掺入率。亚油酸的效果比其他ω-6脂肪酸大约高三倍。随着血浆游离亚油酸或花生四烯酸浓度的增加，观察到典型的双曲线底物饱和曲线。单独灌注时，游离ω-3脂肪酸对肿瘤3H-胸腺嘧啶核苷掺入没有影响，但在亚油酸存在时,ω-3脂肪酸α-亚麻酸（C18:3，N-3）和二十碳五烯酸（C20:5，N-3）竞争性抑制肿瘤亚油酸摄取以及对3H-胸腺嘧啶核苷掺入的刺激作用。结果表明，宿主动脉血中环境血浆游离亚油酸和花生四烯酸浓度直接影响肿瘤DNA合成速率。血浆游离ω-3脂肪酸似乎通过竞争性抑制亚油酸摄取来调节亚油酸的作用。这些关系可以解释饮食中亚油酸和ω-3脂肪酸对体内肿瘤生长的作用。
