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METABOLISM OF SOYBEAN ISOFLAVONOIDS AND LIGNANS IN MAN

大豆异黄酮和木脂素在人体中的代谢

基本信息

批准号：
2633830
负责人：
CARL H ADLERCREUTZ
金额：
$ 14.46万
依托单位：
UNIVERSITY OF HELSINKI
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-09-30 至 1998-12-31
项目状态：
已结题

项目摘要

Soybeans have been found to contain both isoflavonoids and lignans. These diphenolic compounds have in numerous experiments in vitro with cell cultures and in animal experiments been shown to have antiproliferative properties with regard to many types of cancer and have been shown to stimulate differentiation of many leukemic cell lines. In addition they have many other biological effects making them strong candidates for a role as cancer protective agents. The aim of the present investigation is to continue to develop methodology for quantitative measurements of lignans and isoflavonoids in human biological fluids and food specimens using immunological and GC-MS techniques. Polyclonal and monoclonal antibodies will be produced for genistein, daidzein, equol and enterolactone. The main goal is to simplify the techniques making it possible to study larger populations. When these methods are ready it is intended to measure these compounds in already collected plasma samples of groups of young and old women consuming different types of habitual diets (lactovegetarians, omnivores) and two groups of women having been operated for early breast cancer. These samples are unique because we have complete dietary records and assay results for isoflavonoids and lignans in urine as well as for a great number of other steroid and peptide hormones in plasma, urine and feces (more than 50 components). Furthermore it is intended to continue studies on the antiproliferative effects and mechanism of action of phytoestrogens including mammalian lignans and their precursors, which have been synthesized by us, on malignant cell lines using modern techniques. We intend to study particularly human breast, prostate, endometrium and liver cancer cells. These studies will be carried out by adding the compounds alone to cell cultures or in combination or combined with various estrogens, testosterone, antiestrogens, compounds binding to the type II estrogen binding site and antiestrogen binding site, which all have been synthesized already. Simultaneously we measure various proteins like prostatic specific antigen or sex hormone binding globulin in the medium and use molecular biology techniques for clarifying mechanisms. We will also continue the synthesis of reference compounds and deuterium- labelled compounds for GC-MS work as well as labels for time-resolved immunoassay and radioimmunoassay. The work involves synthesis of antigens for production of polyclonal and monclonal antibodies. This laboratory in close collaboration with the Department of Chemistry at the same university since 15 years has provided numerous deuterated and nondeuterated standards of lignans and isoflavonoids to research groups in many countries, mainly to research groups in USA. This we will continue if we can get continuation of the grant support.

已发现蚕豆含有甘草酸和木脂素。这些双酚类化合物在许多体外细胞实验中在培养和动物实验中，与许多类型的癌症有关的性质，并已被证明，刺激许多白血病细胞系分化。此外他们具有许多其他生物学效应，使其成为作为癌症保护剂。本次调查的目的是继续制定方法，人体生物体液和食物标本中的木脂素和木脂素使用免疫学和GC-MS技术。多克隆和单克隆将产生染料木黄酮、大豆苷元、雌马酚和肠内酯。主要目标是简化制作技术可以研究更多的人群。当这些方法准备就绪时，旨在测量已经收集的血浆样品中的这些化合物，年轻和老年妇女群体消费不同类型的习惯性饮食（乳素食者，杂食者）和两组妇女已经手术治疗早期乳腺癌这些样本是独一无二的，因为我们有完整的膳食纪录及尿液中的木脂素及木脂素化验结果以及大量其他类固醇和肽类激素，血浆、尿液和粪便（50多种组分）。更是打算继续研究抗增殖作用，包括哺乳动物木脂素在内的植物雌激素的作用机制，它们的前体，我们已经合成，对恶性细胞，使用现代技术的线条。我们打算特别研究人类乳腺癌、前列腺癌、子宫内膜癌和肝癌细胞。这些研究将通过将化合物单独添加到细胞培养物中或组合或与各种雌激素，睾酮，抗雌激素、结合II型雌激素结合位点的化合物，抗雌激素结合位点，这些都已经被合成了。同时检测前列腺特异性抗原等多种蛋白质或性激素结合球蛋白，并利用分子生物学澄清机制的技术。我们还将继续合成参考化合物和氘- 用于GC-MS工作的标记化合物以及用于时间分辨免疫测定法和放射免疫测定法。这项工作包括合成抗原用于生产多克隆和单克隆抗体。该实验室在与化学系密切合作，同时大学自15年来提供了许多氘和木脂素和木脂素的非氘代标准品，许多国家，主要是美国的研究小组。我们将继续这样做，我们可以继续获得资助。