Department of Environmental and Molecular Toxicology, Oregon State University, ALS 1007, Corvallis, OR, 97331, USA.
Arch Toxicol. 2018 Feb;92(2):571-586. doi: 10.1007/s00204-017-2068-9. Epub 2017 Nov 1.
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that occur in complex mixtures. Several PAHs are known or suspected mutagens and/or carcinogens, but developmental toxicity data is lacking for PAHs, particularly their oxygenated and nitrated derivatives. Such data are necessary to understand and predict the toxicity of environmental mixtures. 123 PAHs were assessed for morphological and neurobehavioral effects for a range of concentrations between 0.1 and 50 µM, using a high throughput early-life stage zebrafish assay, including 33 parent, 22 nitrated, 17 oxygenated, 19 hydroxylated, 14 methylated, 16 heterocyclic, and 2 aminated PAHs. Additionally, each PAH was evaluated for AHR activation, by assessing CYP1A protein expression using whole animal immunohistochemistry (IHC). Responses to PAHs varied in a structurally dependent manner. High-molecular weight PAHs were significantly more developmentally toxic than the low-molecular weight PAHs, and CYP1A expression was detected in five distinct tissues, including vasculature, liver, skin, neuromasts and yolk.
多环芳烃(PAHs)是广泛存在于环境中的污染物,通常以复杂混合物的形式存在。一些多环芳烃已知或被怀疑具有致突变性和/或致癌性,但多环芳烃,特别是其含氧和含氮衍生物的发育毒性数据却很缺乏。这些数据对于理解和预测环境混合物的毒性是必要的。研究人员使用高通量的早期生命阶段斑马鱼试验,评估了 123 种多环芳烃在 0.1 至 50µM 浓度范围内对形态和神经行为的影响,其中包括 33 种母体多环芳烃、22 种硝化多环芳烃、17 种含氧多环芳烃、19 种羟基化多环芳烃、14 种甲基化多环芳烃、16 种杂环多环芳烃和 2 种氨基化多环芳烃。此外,还通过使用全动物免疫组织化学(IHC)评估 CYP1A 蛋白表达来评估每种多环芳烃的 AHR 激活情况。多环芳烃的反应方式具有结构依赖性。高分子量的多环芳烃比低分子量的多环芳烃更具发育毒性,CYP1A 表达在五个不同的组织中被检测到,包括血管、肝脏、皮肤、神经丘和卵黄。