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Transcriptomics and metabolomics analyses provide insights into the difference in toxicity of benzo[a]pyrene and 6-chlorobenzo[a]pyrene to human hepatic cells

2021; Elsevier BV; Volume: 812; Linguagem: Inglês

10.1016/j.scitotenv.2021.152242

1879-1026

Yun Luo, Baoqin Zhang, Ningbo Geng, Shuai Sun, Xiaoyao Song, Jiping Chen, Haijun Zhang,

Pharmacogenetics and Drug Metabolism

The toxicological information of chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs), as derivatives of PAHs, is still relatively lacking. In this study, a combination of transcriptomics and metabolomics approach was adopted to explore the changes in toxicity to human L02 hepatocytes after chlorination of benzo[a]pyrene (B[a]P) at 6 position. In general, 6-Cl-B[a]P produced a stronger toxicity to human hepatic cells than did parent B[a]P. When exposure concentrations were 5 and 50 nM, 6-Cl-B[a]P caused a weaker transcriptomic perturbation relative to B[a]P, whereas a stronger metabolomic perturbation, a stronger oxidative stress and a stronger inhibition effect on cell viability were caused by 6-Cl-B[a]P than did parent B[a]P. Pathway enrichment analysis indicated that 6-Cl-B[a]P produced a more widely perturbation to metabolic pathways than did B[a]P. Although they both significantly impaired the function of mitochondrial electron transport chain (ETC), the exact mechanism is different. B[a]P suppressed the expression of 20 genes regulating mitochondrial ETC mainly via AhR activation. However, 6-Cl-B[a]P produced a stronger inhibition on the activities of complexes I and V than did B[a]P. Meanwhile, 6-Cl-B[a]P also exhibited a stronger inhibition effect on mitochondrial β oxidation of fatty acid. Furthermore, 6-Cl-B[a]P and B[a]P both significantly disturbed the nucleotide metabolism, glycerophospholipid metabolism and amino acid metabolism in L02 cells.