TY - JOUR
T1 - The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro
AU - Kronborg, Thit Mynster
AU - Hansen, Juliana Frohnert
AU - Rasmussen, Åse Krogh
AU - Vorkamp, Katrin
AU - Nielsen, Claus Henrik
AU - Frederiksen, Marie
AU - Hofman-Bang, Jacob
AU - Hahn, Christoffer Holst
AU - Ramhøj, Louise
AU - Feldt-Rasmussen, Ulla
PY - 2017/6
Y1 - 2017/6
N2 - Background: Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro. Materials and methods: Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures. Results: DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5-98.7%), and cAMP by 95.1% (range: 91.5-98.8%) compared to controls). Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited (p<0.0001, p = 0.0079, and p = 0.0002, respectively). The majority of DE-71 added was found in the cell fraction. No cytotoxicity was found. Conclusions: DE-71 inhibited differentiated thyroid cell functions in a two phase response manner and a concentration-dependent inhibition of Tg and cAMP production, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells.
AB - Background: Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro. Materials and methods: Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures. Results: DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5-98.7%), and cAMP by 95.1% (range: 91.5-98.8%) compared to controls). Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited (p<0.0001, p = 0.0079, and p = 0.0002, respectively). The majority of DE-71 added was found in the cell fraction. No cytotoxicity was found. Conclusions: DE-71 inhibited differentiated thyroid cell functions in a two phase response manner and a concentration-dependent inhibition of Tg and cAMP production, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells.
KW - Adenoma/surgery
KW - Cells, Cultured
KW - Cyclic AMP/metabolism
KW - Dose-Response Relationship, Drug
KW - Drug Evaluation, Preclinical
KW - Endocrine Disruptors/pharmacology
KW - Enzyme-Linked Immunosorbent Assay
KW - Flame Retardants/pharmacology
KW - Halogenated Diphenyl Ethers/pharmacology
KW - Humans
KW - RNA, Messenger/metabolism
KW - Radioimmunoassay
KW - Real-Time Polymerase Chain Reaction
KW - Thyroglobulin/metabolism
KW - Thyroid Gland/drug effects
KW - Thyroid Neoplasms/surgery
KW - Thyroidectomy
U2 - 10.1371/journal.pone.0179858
DO - 10.1371/journal.pone.0179858
M3 - Journal article
C2 - 28644858
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 6
M1 - e0179858
ER -