TY - JOUR
T1 - Development and characterization of a human cell line-based transactivation assay to assess thyroid EDCs
AU - Lee, Seok Hee
AU - Seo, Hyeyeong
AU - Lee, Hee Seok
AU - Park, Yooheon
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/3
Y1 - 2020/3
N2 - Thyroid hormones (THs) are one of the most important hormones, playing key roles in the regulation of various physiological functions. Although THs have important function in human, in vitro test methods based on human cells are currently insufficient to effectively screen and test TH-related endocrine disrupting chemicals (EDCs). We established a TH agonist TA assay using the adenocarcinomic human alveolar basal epithelial cell line A549 to test and screen potential TH agonists. To establish the TH agonist TA assay, a TRE-secNluc-IRES-EGFP reporter cassette was constructed and transfected into the A549 cell line using a retrovirus. We evaluated the TH agonistic properties of several chemicals which were tested by existing thyroid agonists testing method (OECD GD 207). Comparing the results of the TH agonist TA assay with the OECD GD 207, T3, T4, tiratricol, and tetrac (natural TH and 3,3′,5,5′-tetraiodothyroacetic acid derivatives), which are TH agonists according to the OECD GD 207, also tested positive in the TH agonist TA assay using the A549 cell line. These results suggested that the TH agonist TA assay developed in this study using a human cell line can provide the information, such as accuracy and specificity to TH agonistic properties of chemicals.
AB - Thyroid hormones (THs) are one of the most important hormones, playing key roles in the regulation of various physiological functions. Although THs have important function in human, in vitro test methods based on human cells are currently insufficient to effectively screen and test TH-related endocrine disrupting chemicals (EDCs). We established a TH agonist TA assay using the adenocarcinomic human alveolar basal epithelial cell line A549 to test and screen potential TH agonists. To establish the TH agonist TA assay, a TRE-secNluc-IRES-EGFP reporter cassette was constructed and transfected into the A549 cell line using a retrovirus. We evaluated the TH agonistic properties of several chemicals which were tested by existing thyroid agonists testing method (OECD GD 207). Comparing the results of the TH agonist TA assay with the OECD GD 207, T3, T4, tiratricol, and tetrac (natural TH and 3,3′,5,5′-tetraiodothyroacetic acid derivatives), which are TH agonists according to the OECD GD 207, also tested positive in the TH agonist TA assay using the A549 cell line. These results suggested that the TH agonist TA assay developed in this study using a human cell line can provide the information, such as accuracy and specificity to TH agonistic properties of chemicals.
KW - A549 cell line
KW - Thyroid hormone associated endocrine disrupting chemicals
KW - Thyroid hormone receptor-mediated transactivation assay
UR - http://www.scopus.com/inward/record.url?scp=85077435596&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2020.109110
DO - 10.1016/j.envres.2020.109110
M3 - Article
C2 - 31918317
AN - SCOPUS:85077435596
SN - 0013-9351
VL - 182
JO - Environmental Research
JF - Environmental Research
M1 - 109110
ER -