Mechanisms of resistance of aquatic vertebrates to PAHs & metal contaminants

由于多氯联苯、二恶英和重金属污染，哈德逊河河口包含超级基金站点，在河口下游的工业化和城市站点的沉积物中多环芳烃水平升高。耐药性是长期接触这些超级基金污染物对居住的野生动物种群的潜在影响之一。虽然抗药性在短期内可能对受影响的种群有利，但受影响的种群可能会增加进化成本，污染物的营养转移可能会危及生态群落的健康。在受到超级基金毒物高度污染的哈德逊河和其他大西洋海岸河口的野生鱼类种群中，观察到对细胞色素P4501A1(CYP1A1)诱导的抗性。在以前的研究中，我们已经记录了来自哈德逊河的一条前哨大西洋鳕鱼(Microgadus Tomcod)的CYP1A1转录诱导能力受损，这些鳕鱼用卤代芳烃化合物(多氯联苯和2，3，7，8-TCDD)处理，但不用非卤化多环芳烃处理。这项研究将集中在我们观察到的鳕鱼中CYP1A1非诱导的机制基础上。我们的工作假设是，在受到Superfund污染的地点，西鳕鱼和其他脊椎动物中的芳香烃受体(AhR)途径下调，从而抑制了CYP1A1的转录。由于AhR的表达在没有芳香烃的情况下对正常的肝脏发育和免疫监控至关重要，因此在超级基金站点修复后，AhR的下调可能会对种群和社区福祉产生深远的影响。我们将初步确定CYP1A1的诱导能力受损是遗传适应还是单代生理适应。我们将使用我们最近开发的Tomcod AhR探针来比较化学处理和环境暴露对哈德逊河和加拿大一条更清洁的参考河Tomcod AhR mRNA和蛋白表达的影响。此外，还将研究金属诱导的甲基化对鳕鱼细胞色素P1A1表达的表观遗传效应。将利用与环境有关的多氯联苯和多环芳烃浓度对先前确定的鳕鱼AhR变异体进行表征，并评估其功能意义。最后，将评估对超级基金污染物的概率响应。这些研究将为野生种群对超级基金化学品混合物的毒性效应的易感性提供新的见解。

The Hudson River estuary contains Superfund sites because of PCB, dioxin, and heavy metal contamination and levels of PAHs are elevated in sediments at industrialized and urban sites in the lower estuary. Resistance is one of the potential effects of chronic exposure to these Superfund contaminants on resident feral populations. While resistance may be beneficial in the short term to impacted populations, evolutionary costs may accrue to affected populations and trophic transfer of contaminants may compromise the health of ecological communities. Resistance to cytochrome P4501A1 (CYP1A1) induction has observed in feral fish populations from the Hudson River and other Atlantic coast estuaries that are highly contaminated with Superfund toxicants. In previous studies, we have documented impaired inducibility of CYP1A1 transcription in a sentinel, Atlantic tomcod (Microgadus tomcod) from the Hudson River, that are treated with halogenated aromatic hydrocarbon compounds (PCBs and 2,3,7,8-TCDD), but not with non-halogenated PAHs. This study will focus on the mechanistic bases of non-inducibility of CYP1A1 in tomcod that we have observed. Our working hypothesis is that CYP1A1 transcription is inhibited by down-regulation of the aromatic hydrocarbon receptor (AhR) pathway in tomcod and other vertebrate species from Superfund contaminated sites. Because AhR expression is critical to normal liver development and immunosurveillance in the absence of aromatic hydrocarbons, down- regulation of AhR may have profound effects on population and community well-being after remediation of Superfund sites. We will initially determine if impaired inducibility of CYP1A1 is a genetic adaptation or a single generation physiological acclimation. We will use our recently developed tomcod AhR probes to compare the effects of chemical treatment and environmental exposure on expression of AhR mRNA and protein in tomcod from the Hudson River and a cleaner reference river in Canada. Additionally, the epigenetic effects of metals- induced methylation will be investigated on expression of CYP1A1 im tomcod. Previously identified tomcod AhR variants will be characterized and their functional significance evaluated with environmentally relevant concentrations of PCBs and PAHs. Finally, a response of probabilities to Superfund contaminants will be evaluated. These studies will provide new insights into the susceptibilities of feral populations to the toxic effects of mixtures of Superfund chemicals.