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哺乳动物木脂素肠内酯和肠二醇及其代谢前体在体外不同终点的遗传毒性研究。

Studies on the genotoxicity of the mammalian lignans enterolactone and enterodiol and their metabolic precursors at various endpoints in vitro.

作者信息

Kulling S E, Jacobs E, Pfeiffer E, Metzler M

机构信息

Department of Chemistry, University of Karlsruhe, Germany.

出版信息

Mutat Res. 1998 Aug 7;416(1-2):115-24. doi: 10.1016/s1383-5718(98)00082-5.

DOI:10.1016/s1383-5718(98)00082-5
PMID:9725997
Abstract

The mammalian lignans enterolactone (ENL) and enterodiol (END) are formed by intestinal bacteria from the plant lignans matairesinol (MAT) and secoisolariciersinol (SEC), respectively, which are ingested with different types of food. ENL and END are weak estrogens. According to epidemiological and biochemical studies, lignans may act as anticarcinogens, but little is known about their genotoxic potential. We have therefore investigated the effects of ENL, END, MAT and SEC on cell-free microtubule assembly and at the following genetic endpoints in cultured male Chinese hamster V79 cells: disruption of the cytoplasmic microtubule complex, induction of mitotic arrest, induction of micronuclei and their characterization by CREST staining, and mutagenicity at the HPRT gene locus. The lignans were tested at concentrations of 200 microM in the cell-free system and 100 microM in cultured cells, which represents the limit of solubility in each assay. The established aneuploidogen diethylstilbestrol and the clastogen 4-nitroquinoline-N-oxide were used as positive reference compounds. As none of the four lignans had any activity at the endpoints studied, we conclude that ENL, END, MAT and SEC are devoid of aneuploidogenic and clastogenic potential under the experimental conditions used in this study.

摘要

哺乳动物木脂素肠内酯(ENL)和肠二醇(END)分别由肠道细菌从植物木脂素开环异落叶松脂素(MAT)和异落叶松脂素(SEC)转化而来,这两种植物木脂素可通过摄入不同类型的食物获得。ENL和END是弱雌激素。根据流行病学和生化研究,木脂素可能具有抗癌作用,但对其遗传毒性潜力了解甚少。因此,我们研究了ENL、END、MAT和SEC对无细胞微管组装的影响,以及在培养的雄性中国仓鼠V79细胞中的以下遗传终点:细胞质微管复合体的破坏、有丝分裂停滞的诱导、微核的诱导及其通过着丝粒蛋白(CREST)染色的表征,以及次黄嘌呤磷酸核糖转移酶(HPRT)基因位点的致突变性。在无细胞系统中以200微摩尔浓度、在培养细胞中以100微摩尔浓度对木脂素进行测试,这代表了每种测定方法中的溶解度极限。已确立的非整倍体诱导剂己烯雌酚和断裂剂4-硝基喹啉-N-氧化物用作阳性参考化合物。由于四种木脂素在所研究的终点均无任何活性,我们得出结论,在本研究使用的实验条件下,ENL、END、MAT和SEC没有非整倍体诱导和断裂潜力。

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