Effect of interleukin (IL)-8 on benzo[a]pyrene metabolism and DNA damage in human lung epithelial cells

Q. Shi, A. W. Boots, L. Maas, C. Veith, K. van Kuijk, G. R. Haenen, R. W. Godschalk, F. J. Van Schooten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

It has been well established that inflammation and concurrent mutagenic exposures drive the carcinogenic process in a synergistic way. To elucidate the role of the inflammatory cytokine IL-8 in this process, we studied its effect on the activation and deactivation of the chemical mutagen benzo[a]pyrene B[a]P in the immortalized pulmonary BEAS-2B cell line. After 24 h incubation with B[a]P in the presence or absence of IL-8, the B[a]P induced cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1) gene expression and CYP1A1 enzyme activity was significantly higher in the presence of the cytokine. Consistent with these findings, we observed higher concentration of the metabolite B[a]P-7,8-diol under concurrent IL-8 treatment conditions. Interestingly, we also found higher concentrations of unmetabolized B[a]P. To explain this, we examined the downstream effects of IL-8 on NADPH oxidases (NOXes). IL-8 lowered the intracellular NADPH level, but this effect could not explain the changes in B[a]P metabolism. IL-8 also significantly depleted intracellular glutathione (GSH), which also resulted in enhanced levels of unmetabolized B[a]P, but increased concentrations of the metabolite B[a]P-7,8-diol. No differences in B[a]P-DNA adducts level were found between B[a]P and B[a]P combined with IL-8, and this might be due to a 3-fold increase in nucleotide excision repair (NER) after IL-8 treatment. These findings suggest that IL-8 increased the formation of B[a]P-7,8-diol despite an overall delayed B[a]P metabolism via depletion of GSH, but DNA damage levels were unaffected due to an increase in NER capacity. (C) 2017 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)64-74
Number of pages11
JournalToxicology
Volume381
DOIs
Publication statusPublished - 15 Apr 2017

Keywords

  • Benzo[a]pyrene (B[a]P)
  • Interleukin (IL)-8
  • NADPH-dependent cytochrome P450s 1A1/
  • 1B1 (CYP1A1/CYP1B1)
  • NADPH oxidase pathway (NOX)
  • Glutathione (GSH)
  • DNA adducts
  • NUCLEOTIDE EXCISION-REPAIR
  • FACTOR-KAPPA-B
  • POLYCYCLIC AROMATIC-HYDROCARBONS
  • OBSTRUCTIVE PULMONARY-DISEASE
  • OXIDATIVE STRESS
  • INFLAMMATORY RESPONSE
  • TRANSCRIPTION FACTOR
  • AIRWAY INFLAMMATION
  • GENE-EXPRESSION
  • ADDUCT LEVELS

Cite this