Establishing a Genetically Stable COS7-RXRα Cell Model for Screening Emerging Contaminants with RXRα Modulatory...

Retinoid X receptor alpha subtype (RXRα) is a multifunctional and essential transcription factor, regulating vital physiological processes. Exploring the (ant)agonistic activities of emerging contaminants by targeting RXRα would provide a new perspective for evaluating their toxicological effects. Considering the limitations of existing methods for rexinoid search, a genetically stable cell line of COS7-RXRα was developed in the present study by dual transduction of the receptor plasmid of pCMV-RXRA and reporter vector of pRXRE-TA-LUC2 in the COS7 cells. After optimization, this COS7-RXRα cell-based assay was validated for its high efficiency in testing RXRα modulatory effects by the S-shaped and inverted S-shaped dose-response curves of the known agonists and antagonists, respectively. Screening the effects of three types of emerging contaminants on RXRα activation showed that butyltins and phenyltins exhibited different extents of agonistic activities, while polyfluorinated iodine alkanes (PFIs) exerted varying degrees of antagonistic potentials. The molecular docking analysis confirmed their interactions with RXRα via the formation of hydrophobic and hydrogen bonds. This developed genetically stable COS7-RXRα cell model would provide a sensitive and robust tool for the high-throughput screening of emerging contaminants with RXRα modulatory effects, expanding new knowledge of their potential endocrine-disrupting effects by targeting RXRα.