[Study on the transcriptional modulation of cytochrome P450 3A4 expression by zearalenone].
OBJECTIVE
To 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).


METHODS
Transient 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.


RESULTS
The 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.


CONCLUSIONS
ZEA 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.
Sun
Jian-han
JH
Department of Toxicology, Zhejiang University, Hangzhou 310031, China.
Zhu
Hui-juan
HJ
Zheng
Yi-fan
YF
Zhu
Xin-qiang
XQ
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D015025:Zearalenone / Q000494:pharmacology*
D015025:Zearalenone; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human