Southern California Coastal Water Research Project Authority (SCCWRP), Costa Mesa, California, USA.
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, USA.
Environ Toxicol Chem. 2018 Mar;37(3):884-892. doi: 10.1002/etc.4024. Epub 2018 Jan 16.
High-throughput cell assays that detect and integrate the response of multiple chemicals acting via a common mode of action have the potential to enhance current environmental monitoring practices. Establishing the linkage between in vitro and in vivo responses is key to demonstrating that in vitro cell assays can be predictive of ecologically relevant outcomes. The present study investigated the potency of 17β-estradiol (E2), estrone (E1), nonylphenol (NP), and treated wastewater effluent using the readily available GeneBLAzer estrogen receptor transactivation assay and 2 life stages of the inland silverside (Menidia beryllina). In vitro estrogenic potencies were ranked as follows: E2 > E1 >> NP. All 3 model estrogens induced vitellogenin and choriogenin expression in a dose-dependent manner in larvae and juveniles. However, apical effects were only found for E2 and E1 exposures of juveniles, which resulted in female-skewed sex ratios. Wastewater effluent samples exhibiting low in vitro estrogenicity (below the 10% effective concentration [EC10]), did not cause significant changes in M. beryllina. Significant induction of estrogen-responsive genes was observed at concentrations 6 to 26 times higher than in vitro responses. Gonadal feminization occurred at concentrations at least 19 to 26 times higher than the in vitro responses. These findings indicated that in vitro cell assays were more sensitive than the fish assays, making it possible to develop in vitro effect thresholds protective of aquatic organisms. Environ Toxicol Chem 2018;37:884-892. © 2017 SETAC.
高通量细胞测定法可检测和整合多种通过共同作用模式发挥作用的化学物质的反应，从而有可能增强当前的环境监测实践。建立体外和体内反应之间的联系是证明体外细胞测定法可以预测具有生态相关性的结果的关键。本研究使用现成的 GeneBLAzer 雌激素受体转录激活测定法和内陆银汉鱼（Menidia beryllina）的 2 个生活阶段，研究了 17β-雌二醇（E2）、雌酮（E1）、壬基酚（NP）和处理后的废水污水的效力。体外雌激素效力的排名如下：E2>E1>>NP。所有 3 种模型雌激素均以剂量依赖性方式在幼虫和幼鱼中诱导卵黄蛋白原和壳蛋白原的表达。然而，仅在幼鱼中发现 E2 和 E1 暴露会产生顶端效应，从而导致雌性偏向的性别比例。表现出低体外雌激素活性（低于 10%有效浓度 [EC10]）的废水污水样本不会导致银汉鱼发生显著变化。在比体外反应高 6 至 26 倍的浓度下观察到雌激素反应基因的显著诱导。性腺女性化发生在比体外反应高至少 19 至 26 倍的浓度下。这些发现表明，体外细胞测定法比鱼类测定法更敏感，从而有可能开发出保护水生生物的体外效应阈值。环境毒理化学 2018；37:884-892。©2017 SETAC。
