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

Konrad A Szychowski,Bartosz Skóra,Marzena Mańdziuk

doi:10.1007/s12640-021-00399-x

Konrad A Szychowski, Bartosz Skóra + Show 1 more

Open Access

https://doi.org/10.1007/s12640-021-00399-x

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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.

Highlights

Tris (2,3-dibromopropyl) isocyanurate, known by its abbreviations TBC or TDBP-TAZTO, is a heterocyclic hexabromated flame retardant
Our experiment shows that, during the differentiation process, the ability of TDBP-TAZTO to induce EROD activity in SH-SY5Y cells decreased successively, which could be an effect of cell differentiation into neurons
Changes observed in EROD activity after stimulation with CAY10464 and βNF correlated with different aryl hydrocarbon receptor (AhR) and cytochrome P450 1A1 (CYP1A1) mRNA expression during differentiation

Summary

Introduction

Tris (2,3-dibromopropyl) isocyanurate, known by its abbreviations TBC or TDBP-TAZTO, is a heterocyclic hexabromated flame retardant. TDBP-TAZTO is widely used in polyolefins, polyphenylalkenes, unsaturated polyester, synthetic rubber, and synthetic fibers (Zhu et al 2012). The first described the use of TDBP-TAZTO dates back to 1959 when it was used in styrene as a flame retardant (Dong et al 2015). Following the cessation of the commercial production of some BFRs and the toxicity of some of these compounds, an increase in TDBP-TAZTO production and use can be expected worldwide, including Europe, the USA, and Japan (Zhu et al 2012)

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