Mechanistic insight into human androgen receptor-mediated endocrine-disrupting potentials by a stable bioluminescence resonance energy transfer-based dimerization assay
- Authors
- Lee, S.-H.; Hong, K.Y.; Seo, H.; Lee, H.-S.; Park, Y.
- Issue Date
- 1-Nov-2021
- Publisher
- Elsevier Ireland Ltd
- Keywords
- Androgen receptor (AR); Bioluminescence resonance energy transfer (BRET); Dimerization assay; Endocrine-disrupting chemicals (EDCs)
- Citation
- Chemico-Biological Interactions, v.349
- Journal Title
- Chemico-Biological Interactions
- Volume
- 349
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/62051
- DOI
- 10.1016/j.cbi.2021.109655
- ISSN
- 0009-2797
1872-7786
- Abstract
- To develop a novel cell-based assay to evaluate the androgenic endocrine-disrupting properties of chemical substances, we established a method to detect ligand-mediated androgen receptor (AR) dimerization in stably transfected human cell lines using a bioluminescence resonance energy transfer (BRET) system. Using stably transfected human embryonic kidney (HEK-293) cells, the BRET-based AR dimerization assay was optimized as a novel test method and was validated using test chemicals recommended by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). The BRET-based AR dimerization assay showed high accuracy, sensitivity, and specificity for the detection of androgenic endocrine-disrupting chemicals (EDCs), and the assay protocol is adequate for practical use. This dimerization assay is based on ligand-mediated hormone receptor dimerization and can provide accurate information about androgenic endocrine-disrupting properties at the cellular level, complementing conventional binding and transactivation assays. © 2021 Elsevier B.V.
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