The toxicities of many environmental polycyclic aromatic hydrocarbons (PAHs), in particular those of high-molecular-weight PAHs (with MW higher than 300), remain poorly characterized. The objective of this study was to evaluate the ability of selected environmentally relevant PAHs with MW 302 (MW302 PAHs) to activate the aryl hydrocarbon receptor (AhR), since this represents a major toxic mode of action of PAHs. A large number of the evaluated compounds exhibited strong AhR-mediated activities, in particular in human models. The studied MW302 PAHs also significantly contributed to the overall calculated AhR activities of complex environmental mixtures, including both defined standard reference materials and collected diesel exhaust particles. The high AhR-mediated activities of representative MW302 PAHs, e.g. naphtho[1,2-k]fluoranthene, corresponded with the modulation of expression of relevant AhR target genes in a human lung cell model, or with the AhR-dependent suppression of cell cycle progression/proliferation in estrogen-sensitive cells. This was in a marked contrast with the limited genotoxicity of the same compound(s). Given the substantial levels of the AhR-activating MW302 PAHs in combustion particles, it is important to continue to investigate the toxic modes of action of this large group of PAHs associated with airborne particulate matter.

许多环境多环芳烃（PAH）的毒性，特别是高分子量PAH（MW高于300）的毒性仍然很差。这项研究的目的是评估具有MW 302（MW302 PAHs）的与环境相关的PAHs激活芳基烃受体（AhR）的能力，因为这代表了PAHs的主要毒性作用方式。大量评估的化合物表现出很强的AhR介导的活性，尤其是在人类模型中。所研究的MW302 PAHs还对复杂环境混合物的总体计算AhR活性做出了重要贡献，包括确定的标准参考物质和收集的柴油机废气颗粒。代表性的MW302 PAHs的高AhR介导的活性，例如萘[1,2- k荧蒽与人类肺细胞模型中相关AhR靶基因表达的调节相对应，或与雌激素敏感性细胞中细胞周期进程/增殖的AhR依赖性抑制有关。这与相同化合物有限的遗传毒性形成鲜明对比。考虑到燃烧颗粒中大量激活AhR的MW302 PAH，重要的是要继续研究与空气中颗粒物相关的大量PAH的毒性作用方式。