Diversified expression of aryl hydrocarbon receptor dependent genes in human laryngeal squamous cell carcinoma cell lines treated with β-naphthoflavone

Toxicol Lett. 2014 Nov 18;231(1):99-107. doi: 10.1016/j.toxlet.2014.09.005. Epub 2014 Sep 8.

Abstract

The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous environmental pollutants. In this study the effect of administration of β-naphthoflavone (BNF), potent AhR ligand, on the expression of AhR, AhRR, CYP1A1, CYP1A2, CYP1B1, NQO1, GSTA1, ALDH3A1 and UGT1A genes encoding the enzymes controlled by AhR were examined in thirteen laryngeal tumor cell lines and in HepaRG cell line. The analyzed cell lines were derived from patients with squamous laryngeal cancer, with history of cigarette smoking and without signs of human papillomavirus types 16 and 18 infection in investigated cells. Quantitative real-time RT-PCR analysis revealed huge interindividual differences in expression of genes from AhR regulatory network. Our results strongly suggest predominant effect of DNA methylation on induction of CYP1A1 expression by AhR ligands as well. Our results indicate that differentiated HepaRG cell line appeared to be very good substitute for human liver in studies on xenobiotic metabolism by AhR regulated enzymes.

Keywords: AhR; AhRR; CYP1A1; CYP1A2; CYP1B1; GSTA1; NQO1; SCC cell lines; UGT1A1; β-naphthoflavone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / agonists*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Carcinogens, Environmental / toxicity*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Cytochrome P-450 CYP1A1 / genetics
  • DNA Methylation / drug effects
  • Enzyme Induction
  • Epigenesis, Genetic / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / metabolism*
  • Ligands
  • Long Interspersed Nucleotide Elements / drug effects
  • Real-Time Polymerase Chain Reaction
  • Receptors, Aryl Hydrocarbon / agonists*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • beta-Naphthoflavone / toxicity*

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinogens, Environmental
  • Ligands
  • Receptors, Aryl Hydrocarbon
  • beta-Naphthoflavone
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1