First evidence of estrogenic potential of the cyanobacterial heptotoxins the nodularin-R and the microcystin-LR in cultured mammalian cells
First evidence of estrogenic potential of the cyanobacterial heptotoxins the nodularin-R and the microcystin-LR in cultured mammalian cells
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DOI：
10.1016/j.jhazmat.2009.09.095
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发表时间：
2010-02-15
影响因子：
13.6
通讯作者：
Bouaicha, Noureddine
中科院分区：
文献类型：
--
作者：
Oziol, Lucie;Bouaicha, Noureddine
本文首次研究了蓝藻肝毒素微囊藻毒素-LR(MC-LR)和结节菌素-R(NOD-R)在稳定表达雌激素荧光素酶基因的细胞系中的雌激素样活性。用NOD-R处理细胞后，荧光素酶活性呈剂量依赖性增加。NOD-R诱导荧光素酶活性，EC50值为66.4 nM。而阳性对照17β-雌二醇(E-2)的EC50为9.6 pm这表明NOD-R是荧光素酶的诱导剂，比E2弱6900倍。相比之下，MC-LR在2.01-60.1 nM之间仅观察到轻微但显著的荧光素酶基因激活，并在10.1 nM时观察到最大诱导反应，约为1 nM E2最大诱导效应的25%。高MC-LR浓度下荧光素酶活性的下降可以用细胞毒效应来解释。当每种毒素与雌二醇单用时，未观察到协同雌激素效应。然而，NOD-R和MC-LR对荧光素酶活性的诱导可被1mU M的纯雌激素受体(ER)拮抗剂ICI 182.780抑制，从而证明雌激素效应的ER依赖性。(C)2009爱思唯尔B.V.保留所有权利。
The estrogenic activity of cyanobacterial hepatotoxins microcystin-LR (MC-LR) and nodularin-R (NOD-R) was for the first time investigated in vitro in a stably transfect cell line with an estrogen-regulated luciferase gene. Treatment of cells with NOD-R caused a dose-dependent increase in the luciferase activity. NOD-R gave rise to an induction of luciferase activity with an EC50 value of 66.4 nM. whereas the positive control, 17 beta-estradiol (E-2) had an EC50 of 9.6 pM. This indicates that NOD-R is a 6900-fold weaker inducer of luciferase than E2. In contrast, only a slight but significant activation of the luciferase gene was observed with MC-LR between 2.01 and 60.1 nM, and a maximal-induced response was observed with 10.1 nM, approximately 25% of the maximal effect obtained with 1 nM E2. The decrease in the luciferase activity at high MC-LR concentrations can be explained by a cytotoxic effect. No synergistic estrogenic effect was observed when each toxin was co-administrated with E2. However, the induction of the luciferase activity by NOD-R and MC-LR was inhibited by co-treatment with 1 mu M of the pure estrogenic receptor (ER) antagonist ICI 182.780, thus proving the ER-dependency of the estrogenic effect. (C) 2009 Elsevier B.V. All rights reserved.