An In Vitro Bioassay for Xenobiotics Using the SXR-Driven Human CYP3A4/lac Z Reporter Gene

The dose and time effect of nine xenobiotics, including 17β-estradiol, corticosterone, dexamethasone, progesterone, nifedipine, bisphenol A, rifampicin, methamphetamine, and nicotine were investigated, in vitro, using human steroid and xenobiotics receptor (SXR)-binding sites on the human CYP3A4 promoter, which can enhance the linked lac Z reporter gene transcription. To test this, liver-specific SAP (human serum amyloid P component)-SXR (SAP/SXR) and human CYP3A4 promoter-regulated lac Z (h CYP3A4/lac Z) constructs were transiently transfected into Hep G2 and NIH3T3 cells to compare the xenobiotic responsiveness between human and nonhuman cell lines. In the Hep G2 cells, rifampicin, followed by corticosterone, nicotine, methamphetamine, and dexamethasone, exhibited enhanced levels of the lac Z transcript, whereas those of bisphenol A and nifedipine were found to be reduced. No significant responses were observed with 17β-estradiol or progesterone. In addition, 17β-estradiol and progesterone did not chang...