Wilson Lindsay B, Moran Ian L, Anderson Kim A, Tanguay Robyn L
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331.
Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR 97333.
Curr Opin Toxicol. 2023 Jun;34. doi: 10.1016/j.cotox.2023.100392. Epub 2023 Mar 11.
Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds produced by a variety of petrogenic and pyrogenic sources. PAHs inherently occur in the environment in complex mixtures. The early life-stage zebrafish model is a valuable tool for high-throughput screening (HTS) for toxicity of complex chemical mixtures due to its rapid development, high fecundity, and superb sensitivity to chemical insult. Zebrafish are amenable to exposure to surrogate mixtures as well as extracts of environmental samples and effect-directed analysis. In addition to its utility to HTS, the zebrafish has proven an excellent model for assessing chemical modes of action and identifying molecular initiating and other key events in an Adverse Outcome Pathway framework. Traditional methods of assessing PAH mixture toxicity prioritize carcinogenic potential and lack consideration of non-carcinogenic modes of action, assuming a similar molecular initiating event for all PAHs. Recent work in zebrafish has made it clear that while PAHs belong to the same chemical class, their modes of action can be divergent. Future research should use zebrafish to better classify PAHs by their bioactivity and modes of action to better understand mixture hazards.
多环芳烃（PAHs）是一类由多种石油成因和热成因来源产生的有机化合物。PAHs在环境中天然以复杂混合物的形式存在。斑马鱼幼体模型因其发育迅速、繁殖力高以及对化学损伤极为敏感，是用于高通量筛选（HTS）复杂化学混合物毒性的宝贵工具。斑马鱼适合接触替代混合物以及环境样品提取物和效应导向分析。除了在高通量筛选方面的用途外，斑马鱼已被证明是评估化学作用模式以及在不良结局途径框架中识别分子引发事件和其他关键事件的优秀模型。传统的评估PAH混合物毒性的方法将致癌潜力作为优先考量因素，并且没有考虑非致癌作用模式，假定所有PAHs都有相似的分子引发事件。斑马鱼的最新研究表明，虽然PAHs属于同一化学类别，但其作用模式可能不同。未来的研究应该利用斑马鱼根据其生物活性和作用模式更好地对PAHs进行分类，以便更好地了解混合物危害。
