DNA fragmentation, apoptosis and cell cycle arrest induced by zearalenone in cultured DOK, Vero and Caco-2 cells: prevention by Vitamin E
DNA fragmentation, apoptosis and cell cycle arrest induced by zearalenone in cultured DOK, Vero and Caco-2 cells: prevention by Vitamin E
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DOI：
10.1016/s0300-483x(03)00329-9
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发表时间：
2003-11-05
期刊：
影响因子：
4.5
通讯作者：
Bacha, H
中科院分区：
文献类型：
--
作者：
Abid-Essefi, S;Baudrimont, I;Bacha, H
玉米赤霉烯酮(Zearalenone，ZEN)是一种非甾体类雌激素类真菌毒素，由多种禾谷类镰刀菌产生。ZEN及其代谢物与人的雌激素受体结合，因此表现出雌激素和合成代谢的特性。多项研究表明，Zen在体内可能具有遗传毒性。Zen在枯草芽孢杆菌重组试验中损伤DNA，并诱导CHO细胞姐妹染色单体互换和染色体畸变。ZEN还可以诱导小鼠组织中DNA加合物的形成和溶原菌的SOS修复过程。在目前的研究中，已经证实了Zen在三个细胞系Vero中的遗传毒性。Caco-2和DOK的浓度分别为10、20和40微米。在此条件下，Zen诱导浓度依赖的DNA片段化，导致DNA在琼脂糖凝胶上出现梯状条带。这一观察结果与细胞凋亡是一致的。观察到凋亡小体的形成，证实了这一点。此外，Zen诱导了三种细胞系的细胞周期停滞，其特征是细胞周期中处于G2/M期的细胞数量增加。同时加入维生素E(25um)和Zen可部分减少孵育24 h后DNA片段化和凋亡体的形成。维生素E可能通过维持长时间的细胞周期停滞来发挥作用，在此期间DNA修复发生。(C)2003爱思唯尔爱尔兰有限公司。保留所有权利。
Zearalenone (ZEN) is a non-steroidal oestrogenic mycotoxin produced by several Fusarium species growing on cereals. ZEN and its metabolites bind to human oestrogen receptors and hence display oestrogenic and anabolic properties. Several lines of investigation suggest that ZEN may be genotoxic in vivo. ZEN damages DNA in Bacillus subtilis recombination tests, and it induces sisterchromatid exchange and chromosomal aberration in CHOcells. ZEN also induces DNA-adduct formation in mouse tissues and SOS repair process in lysogenic bacteria. In the present study, ZEN genotoxicity has been confirmed in three cell-lines, Vero. Caco-2 and DOK at concentrations of 10, 20 and 40 muM. Under these conditions, ZEN induces concentration-dependent DNA fragmentation resulting in DNA laddering patterns on agarose get electrophoresis. This observation is consistent with apoptosis. which was confirmed by observations of formation of apoptotic bodies. Moreover, ZEN induces cell cycle arrest in the three cell-lines characterised by an increase of the number of cells in the G2/M phase of the cell cycle. Vitamin E (25 muM) added simultaneously with ZEN partially reduces DNA fragmentation and apoptotic body formation after 24 h incubation. Vitamin E may act by maintaining prolonged cell cycle arrest during which time DNA repair takes place. (C) 2003 Elsevier Ireland Ltd. All rights reserved.