Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells

Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells
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DOI:
10.1007/s10616-012-9476-8
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发表时间:
2013-03-01
期刊:
影响因子:
2.2
通讯作者:
Mantovani, Mario Sergio
Mantovani, Mario Sergio
中科院分区:
生物学4区
文献类型:
--
作者:
Lepri, Sandra Regina;Luiz, Rodrigo Cabral;Mantovani, Mario Sergio

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异黄酮类化合物是广泛存在于植物中的酚类化合物,在大豆中含量很高。它们具有重要的生物学特性,被认为是潜在的化学预防药物。本研究的目的是通过微核试验、GST活性分析和实时定量RT-PCR检测GSTa2基因的表达来验证两种大豆异黄酮(染料木素和大豆苷元)的预防作用。使用直接(阿霉素)和间接(2-氨基蒽)DNA损伤的诱变剂。用金雀异黄素或大豆苷元处理人肝癌细胞(HTC)26h,分别用10mU M单独作用,0.1、1.0和10mU M与遗传毒性药物联合作用。微核试验表明,两种异黄酮单用均无遗传毒性作用。染料木素对直接和间接DNA损伤剂均有抗突变作用。在第二时相酶调节方面,本研究表明,在10MU M添加染料木素和大豆苷元时,细胞质总GST活性增加。然而,染料木素和大豆苷元对GSTa2同工酶的mRNA水平无明显影响。结果表明,金雀异黄素具有体外抗直接和间接DNA损伤诱变活性。
Isoflavones are phenolic compounds widely distributed in plants and found in a high percentage in soybeans. They have important biological properties and are regarded as potential chemopreventive agents. The aim of this study was to verify the preventive effect of two soy isoflavones (genistein and daidzein) by a micronucleus assay, analysis of GST activity, and real-time RT-PCR analysis of GSTa2 gene expression. Mutagens of direct (doxorubicin) and indirect (2-aminoanthracene) DNA damage were used. Hepatoma cells (HTC) were treated with genistein or daidzein for 26 h at noncytotoxic concentrations; 10 mu M when alone, and 0.1, 1.0 and 10 mu M when combined with genotoxic agents. The micronucleus test demonstrated that both isoflavones alone had no genotoxic effect. Genistein showed antimutagenic effects at 10 mu M with both direct and indirect DNA damage agents. On phase II enzyme regulation, the current study indicated an increase in total cytoplasmic GST activity in response to genistein and daidzein at 10 mu M supplementation. However, the mRNA levels of GSTa2 isozymes were not differentially modulated by genistein or daidzein. The results point to an in vitro antimutagenic activity of genistein against direct and indirect DNA damage-induced mutagenicity.