Polycyclic aromatic hydrocarbons (PAHs) and Chlorinated PAHs (Cl-PAHs) are ubiquitous environmental contaminants. The toxicological information of anthracene (Ant) and its chlorinated derivatives is quite limited. In this study, an integrated metabolomic and transcriptomic analysis approach was adopted to assess the toxic effects triggered by Ant and its chlorinated derivatives, 2-chloroanthracene (2-ClAnt) and 9,10-dichloroanthracen (9,10-Cl₂Ant), at human-relevant levels on human normal hepatocyte L02 cells. The cell viability test showed no significant effects on the viability of L02 cells exposed to Ant, 2-ClAnt and 9,10-Cl₂Ant at doses of 5–500 nM for 24 h. However, based on transcriptomic analysis, Ant, 2-ClAnt and 9,10-Cl₂Ant exposure at human-relevant levels obviously perturbed global gene expression in L02 cells and induced the differential expression of several genes related to cancer development. As the number of genes related to cancer development altered by 9,10-Cl₂Ant is the largest, 9,10-Cl₂Ant posed greater risks of tumor development than Ant and 2-ClAnt did. Metabolomics analysis demonstrated that Ant, 2-ClAnt and 9,10-Cl₂Ant caused significant metabolic perturbation in L02 cells. Pathway enrichment analysis indicated that Ant, 2-ClAnt and 9,10-Cl₂Ant mainly perturbed the lipid metabolism and nucleotide metabolism pathway. However, 9,10-Cl₂Ant caused a wider perturbation to metabolic pathways than Ant and 2-ClAnt did. In addition, dysregulation of nucleotide metabolism perturbed by Ant, 2-ClAnt and 9,10-Cl₂Ant may be associated with the genomic instability and further carcinogenesis.

多环芳烃 (PAH) 和氯化 PAH (Cl-PAH) 是普遍存在的环境污染物。蒽（Ant）及其氯化衍生物的毒理学信息相当有限。在本研究中，采用综合代谢组学和转录组学分析方法来评估Ant及其氯化衍生物2-氯蒽（2-ClAnt）和9,10-二氯蒽（9,10-Cl ₂ Ant）引发的毒性作用。对人类正常肝细胞 L02 细胞的影响达到人类相关水平。细胞活力测试显示，暴露于剂量为 5-500 nM 的Ant、2-ClAnt 和 9,10-Cl ₂ Ant 24 小时后，L02 细胞的活力没有显着影响。然而，基于转录组分析，人类相关水平的Ant、2-ClAnt和9,10-Cl _{2 Ant暴露明显扰乱L02细胞中的整体基因表达，并诱导与癌症发展相关的多个基因的差异表达。由于9,10-Cl 2} Ant改变的与癌症发生相关的基因数量最多，因此9,10-Cl ₂ Ant比Ant和2-ClAnt具有更大的肿瘤发生风险。代谢组学分析表明，Ant、2-ClAnt 和 9,10-Cl ₂ Ant 在 L02 细胞中引起显着的代谢扰动。通路富集分析表明Ant、2-ClAnt和9,10-Cl ₂ Ant主要干扰脂质代谢和核苷酸代谢通路。然而，9,10-Cl ₂ Ant 比 Ant 和 2-ClAnt 对代谢途径造成更广泛的干扰。此外，Ant、2-ClAnt和9,10-Cl ₂ Ant扰乱的核苷酸代谢失调可能与基因组不稳定性和进一步的致癌作用有关。