In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: receptor-based bioassay screens.
In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: receptor-based bioassay screens.
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DOI：
10.1289/ehp.11200
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发表时间：
2008-09
影响因子：
10.4
通讯作者：
Hammock BD
中科院分区：
文献类型：
--
作者：
Ahn KC;Zhao B;Chen J;Cherednichenko G;Sanmarti E;Denison MS;Lasley B;Pessah IN;Kültz D;Chang DP;Gee SJ;Hammock BD
人们对个人护理产品中抗菌剂三氯卡班（TCC）和三氯生（TCS）的生物学和毒理学效应表示担忧。很少有研究评价其在哺乳动物细胞中的生物活性，以评估其潜在的不良影响。在这项研究中，我们在体外核受体反应和钙信号生物测定中评估了TCC及其类似物和TCS的活性。我们确定了化合物的生物活性，在体外，细胞为基础的，和核受体反应性生物测定的受体芳烃（AhR），雌激素（ER），雄激素（AR），和ryanodine（RyR 1）。一些碳酰苯胺化合物，包括TCC（1-10 μM），增强雌二醇（E2）依赖性或睾酮依赖性ER和AR反应基因表达的激活高达2.5倍，但单独显示很少或没有激动活性。一些碳酰苯胺和TCS表现出弱的激动和/或拮抗活性的AhR响应的生物测定。TCS在ER-和AR-反应生物测定中均表现出拮抗活性。TCS（0.1-10 μM）显著增强[3 H]ryanodine与RyR 1的结合，并引起初级骨骼肌肌管静息胞浆[Ca 2 +]升高，但碳酰二苯胺没有影响。包括TCC在内的碳酰胺类化合物增强了ER和AR依赖性基因表达的雌激素依赖性诱导，但几乎没有激动剂活性，这表明了内分泌干扰化合物的一种新的作用机制。TCS，结构上类似于非共面邻位取代的多氯联苯，表现出较弱的AhR活性，但与RyR 1相互作用，并刺激Ca 2+动员。这些观察结果对人类和动物健康具有潜在影响。需要进一步研究TCC及其类似物和TCS的生物学和毒理学效应。
Concerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects. In this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor–responsive and calcium signaling bioassays. We determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor–responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1). Some carbanilide compounds, including TCC (1–10 μM), enhanced estradiol (E2)-dependent or testosterone-dependent activation of ER- and AR-responsive gene expression up to 2.5-fold but exhibited little or no agonistic activity alone. Some carbanilides and TCS exhibited weak agonistic and/or antagonistic activity in the AhR-responsive bioassay. TCS exhibited antagonistic activity in both ER- and AR-responsive bioassays. TCS (0.1–10 μM) significantly enhanced the binding of [3H]ryanodine to RyR1 and caused elevation of resting cytosolic [Ca2+] in primary skeletal myotubes, but carbanilides had no effect. Carbanilides, including TCC, enhanced hormone-dependent induction of ER- and AR-dependent gene expression but had little agonist activity, suggesting a new mechanism of action of endocrine-disrupting compounds. TCS, structurally similar to noncoplanar ortho-substituted poly-chlorinated biphenyls, exhibited weak AhR activity but interacted with RyR1 and stimulated Ca2+ mobilization. These observations have potential implications for human and animal health. Further investigations are needed into the biological and toxicologic effects of TCC, its analogs, and TCS.
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影响因子：
3
作者：
Liu, BQ;Wang, YQ;Anderson, VE
通讯作者：
Anderson, VE
影响因子：
3.4
作者：
Fessenden, JD;Wang, YM;Pessah, IN
通讯作者：
Pessah, IN
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作者：
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影响因子：
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作者：
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3.3
作者：
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通讯作者：
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