Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid.

Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid.
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发表时间:
1990-02
期刊:
影响因子:
11.2
通讯作者:
Y. Ha;J. Storkson;M. Pariza
Y. Ha;J. Storkson;M. Pariza
中科院分区:
医学1区
文献类型:
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作者:
Y. Ha;J. Storkson;M. Pariza

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烤碎牛肉含有抑制7,12-二甲基苯并蒽引发小鼠表皮癌的因子。此前,我们分离出了一种活性成分,并将其表征为亚油酸(CLA)共轭二烯衍生物的异构体混合物。我们现在表明,合成共轭亚油酸抑制小鼠前胃肿瘤的苯并(a)芘的启动。p.o.前4天和2天用苯并(a)芘处理后,雌性ICR小鼠被给予(a)橄榄油中的CLA,(B)橄榄油中的亚油酸,或(c)单独的橄榄油或加0.85%盐水(对照组)。三天后,重复该循环共4次。在30周龄时,处死小鼠。在三个独立的实验中,用CLA治疗的小鼠仅产生了对照组小鼠的肿瘤/动物的一半(P小于0.025);在其中两个实验中,肿瘤发生率也降低了(P小于0.05)。各组之间的摄食量或体重无显著差异。高效液相色谱/气相色谱分析确定,插管后,只有c-9,t-11共轭亚油酸异构体被纳入前胃磷脂。在旨在阐明作用机制的研究中,我们发现CLA是一种有效的抗氧化剂。在测试条件下,CLA比α-生育酚更有效,并且几乎与丁基化羟基甲苯一样有效。这些观察结果表明,共轭亚油酸可能作为一种原位防御机制,对膜攻击的自由基,并可能,至少部分地解释了共轭亚油酸的抗癌特性。
Grilled ground beef contains factors that inhibit the initiation of mouse epidermal carcinogenesis by 7,12-dimethylbenz(a)anthracene. Previously we isolated an active principal and characterized it as an isomeric mixture of conjugated dienoic derivatives of linoleic acid (CLA). We now show that synthetic CLA inhibits the initiation of mouse forestomach tumorigenesis by benzo(a)pyrene. Four and 2 days prior to p.o. treatment with benzo(a)pyrene, female ICR mice were given (a) CLA in olive oil, (b) linoleic acid in olive oil, or (c) olive oil alone or plus 0.85% saline (control groups). Three days later the cycle was repeated for a total of 4 times. At 30 wk of age, the mice were sacrificed. In three independent experiments, mice treated with CLA developed only about half as many neoplasms/animal as mice in the control groups (P less than 0.025); in two of the experiments tumor incidence was also reduced (P less than 0.05). There were no significant differences in food intake or body weight among the groups. High-performance liquid chromatography/gas chromatography analysis established that, following intubation, only the c-9, t-11 CLA isomer was incorporated into forestomach phospholipids. In studies aimed at elucidating the mechanism of action, we found that CLA is an effective antioxidant. Under the conditions of the test CLA was more potent than alpha-tocopherol and almost as effective as butylated hydroxytoluene. These observations indicate that CLA might serve as an in situ defense mechanism against membrane attack by free radicals and may, at least in part, explain the anticarcinogenic properties of CLA.