Transcriptomics and metabolomics analyses provide insights into the difference in toxicity of benzo[a]pyrene and 6-chlorobenzo[a]pyrene to human hepatic cells.
Sci Total Environ
; 812: 152242, 2022 Mar 15.
Article
de En
| MEDLINE
| ID: mdl-34919925
ABSTRACT
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 ß 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Hydrocarbures aromatiques polycycliques
/
Benzo[a]pyrène
Limites:
Humans
Langue:
En
Journal:
Sci Total Environ
Année:
2022
Type de document:
Article
Pays d'affiliation:
Chine