Diamante Graciel, do Amaral E Silva Müller Gabrielle, Menjivar-Cervantes Norma, Xu Elvis Genbo, Volz David C, Dias Bainy Afonso Celso, Schlenk Daniel
Department of Environmental Sciences, University of California, 900 University Ave., Riverside, CA 92521, USA.
Department of Biochemistry, Federal University of Santa Catarina (UFSC), Florianópolis, SC 88040-900, Brazil.
Aquat Toxicol. 2017 Aug;189:77-86. doi: 10.1016/j.aquatox.2017.05.013. Epub 2017 Jun 3.
One of the primary sources of polycyclic aromatic hydrocarbons (PAHs) in marine environments is oil. Photochemical oxidation and microbial transformation of PAH-containing oils can result in the formation of oxygenated products. Among the PAHs in crude oil, chrysene is one of the most persistent within the water column and may be transformed to 2- and 6-hydroxychrysene (OHCHR). Both of these compounds have been shown to activate (2-OHCHR) and antagonize (6-OHCHR) the estrogen receptor (ER). Previous studies in our lab have shown that estrogen can significantly alter zebrafish development. However, little is known about the developmental toxicity of hydroxylated PAHs. Zebrafish embryos were exposed to 0.5-10μM of 2- or 6-OHCHR from 2h post-fertilization (hpf) until 76hpf. A significant decrease in survival was observed following exposure to 6-OHCHR - but not 2-OHCHR. Both OHCHRs significantly increased the percentage of overall deformities after treatment. In addition to cardiac malformations, ocular and circulatory defects were also observed in embryos exposed to both compounds, while 2-OHCHR generally resulted in a higher prevalence of effect. Moreover, treatment with 2-OHCHR resulted in a significant decrease in hemoglobin levels. ER nor G-Protein coupled estrogen receptor (GPER) antagonists and agonists did not rescue the observed defects. We also analyzed the expression of cardiac-, eye- and circulation-related genes previously shown to be affected by oil. Rhodopsin mRNA expresssion was significantly decreased by both compounds equally. However, exposure to 2-OHCHR significantly increased the expression of the hematopoietic regulator, runx1 (runt related transcription factor 1). These results indicate the toxicity of oxygenated photoproducts of PAHs and suggest that other targets and signaling pathways may contribute to developmental toxicity of weathered oil. Our findings also demonstrate the regio-selective toxicity of hydroxy-PAHs in the effects on eye and circulatory development and raise the need to identify mechanisms and ecological risks of oxy-PAHs to fish populations.
海洋环境中多环芳烃（PAHs）的主要来源之一是石油。含PAH的石油发生光化学氧化和微生物转化会导致含氧产物的形成。在原油中的PAHs中，屈是水柱中最持久的物质之一，可能会转化为2-羟基屈和6-羟基屈（OHCHR）。这两种化合物已被证明可激活（2-OHCHR）和拮抗（6-OHCHR）雌激素受体（ER）。我们实验室之前的研究表明，雌激素可显著改变斑马鱼的发育。然而，关于羟基化PAHs的发育毒性知之甚少。将斑马鱼胚胎从受精后2小时（hpf）至76 hpf暴露于0.5 - 10μM的2-OHCHR或6-OHCHR中。暴露于6-OHCHR后观察到存活率显著下降，但2-OHCHR未导致此现象。两种OHCHR处理后均显著增加了总体畸形的百分比。除心脏畸形外，在暴露于这两种化合物的胚胎中还观察到眼部和循环系统缺陷，而2-OHCHR通常导致更高的效应发生率。此外，用2-OHCHR处理导致血红蛋白水平显著下降。ER和G蛋白偶联雌激素受体（GPER）拮抗剂及激动剂均不能挽救所观察到的缺陷。我们还分析了先前显示受石油影响的心脏、眼睛和循环相关基因的表达。视紫红质mRNA表达均被这两种化合物同等程度地显著降低。然而，暴露于2-OHCHR显著增加了造血调节因子runx1（ runt相关转录因子1）的表达。这些结果表明了PAHs含氧光产物的毒性，并表明其他靶点和信号通路可能导致风化油的发育毒性。我们的研究结果还证明了羟基化PAHs在对眼睛和循环系统发育影响方面的区域选择性毒性，并提出需要确定含氧PAHs对鱼类种群的作用机制和生态风险。
