期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 349, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2021.109655
关键词
Endocrine-disrupting chemicals (EDCs); Androgen receptor (AR); Bioluminescence resonance energy transfer (BRET); Dimerization assay
资金
- Ministry of Food and Drug Safety [18163MFDS109]
A novel cell-based assay was developed to evaluate the androgenic endocrine-disrupting properties of chemical substances, using a method to detect ligand-mediated androgen receptor (AR) dimerization in stably transfected human cell lines with a Bioluminescence Resonance Energy Transfer (BRET) system. The BRET-based AR dimerization assay demonstrated high accuracy, sensitivity, and specificity for detecting androgenic endocrine-disrupting chemicals (EDCs) and is suitable for practical use. This assay provides accurate information about androgenic endocrine-disrupting properties at the cellular level and complements conventional binding and transactivation assays.
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.
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