OBJECTIVETo study whether zearalenone (ZEA), a fungal estrogen, can transcriptionally up-regulate the expression of cytochrome 450 3A4 (CYP3A4) transcription by activating human steroid hormone and xenobiotic receptor (SXR).

METHODTransient cotransfection reporter gene assays were performed with human SXR expression plasmid and a reporter plasmid containing the SXR in the CYP3A4 gene promoter in HepG(2) cells.

RESULTSThe transcriptional induction of CYP3A4 by ZEA with a dose, time-dependent manner. ZEA at the concentrations of 0.01, 0.10, 1.00 and 10.00 micromol/L, respectively, could induce CYP3A4 with (1.50 +/- 0.21), (1.66 +/- 0.27), (3.04 +/- 0.82) and (3.96 +/- 1.16) folds, as compared with 0.1% DMSO. Results from a time-dependent study show that 1.00 and 10.00 micromol/L of ZEA for 12 to 48 hours could enhance the transcription of CYP3A4 with (3.69 +/- 1.34) and (5.18 +/- 1.50) folds, and 10.00 micromol/L of ZEA for 48 hours could induce the CYP3A4 gene expression (5.18 +/- 1.50) folds, as compared with 0.1% DMSO by activating human SXR.

CONCLUSIONZEA could induce the expression of the CYP3A4 gene transcription through activating SXR, possibly by affecting the other substrates of the CYP3A4, especially affecting the metabolism of drugs in the body.