Tris (2,3-Dibromopropyl) Isocyanurate (TDBP-TAZTO or TBC) Shows Different Toxicity Depending on the Degree of Differentiation of the Human Neuroblastoma (SH-SY5Y) Cell Line

Neurotox Res. 2021 Oct;39(5):1575-1588. doi: 10.1007/s12640-021-00399-x. Epub 2021 Aug 3.

Abstract

Tris (2,3-dibromopropyl) isocyanurate (TDBP-TAZTO or TBC) is a heterocyclic hexabromated flame retardant. It is widely used during the production of many synthetic compounds. High concentrations of TDBP-TAZTO were found in river water, surface sediments, soil, earthworms, and carp tissues. Moreover, it has been shown that this compound can cross the blood-brain barrier and accumulate in the gut and brain of carp. The aryl hydrocarbon receptor (AhR) has been characterized as a multifunctional intracellular sensor and receptor. AhR is an activator of cytochrome P450 1A1 and 1A2, which metabolize various toxic compounds. The aim of the study was to explain how/whether TDBP-TAZTO increases the expression and/or activity of the CYP1A1 enzyme and the AhR and TUBB3 expression during SH-SY5Y cell differentiation. SH-SY5Y cells were differentiated for 7 and 14 days using retinoic acid. Cell viability, ethoxyresorufin-O-deethylase (EROD) activity, and mRNA expression of CYP1A1, AhR, and TUBB3 were assessed. Our experiment showed that, during the differentiation process, the ability of TDBP-TAZTO to induce EROD activity in SH-SY5Y cells subsequently decreased, which may have been an effect of cell differentiation into neurons. Moreover, the results suggest that TDBP-TAZTO can affect the differentiation process. Since no CYP2B6 mRNA expression was detected, the CAR receptor may not be involved in the TDBP-TAZTO mechanism of action. However, more research is needed in this field to elucidate this mechanism precisely.

Keywords: Differentiation; Flame retardant; Neuron; Retinoic acid; TBC; TDBP-TAZTO.

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Flame Retardants / toxicity*
  • Humans
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology*
  • Organophosphates / toxicity*
  • Reactive Oxygen Species / metabolism
  • Receptors, Aryl Hydrocarbon / metabolism

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Flame Retardants
  • Organophosphates
  • Reactive Oxygen Species
  • Receptors, Aryl Hydrocarbon
  • tris(2,3-dibromopropyl)phosphate