Abstract：
:In the present study, we investigated the inducibility of the drug conjugate transporter genes MRP1 and MRP2 by redox-active compounds such as tertiary butylated hydroquinone (tBHQ) and quercetin and by chemicals known to activate the pregnane X receptor (PXR) such as rifampicin and clotrimazol and by the metalloid compound arsenite. The human MRP2 gene was found to be inducible in HepG2 cells by rifampicin, clotrimazol, arsenite and tBHQ. As MRP1 expression is extremely low in HepG2 cells, its inducibility was studied in MCF-7 cells. However, only tBHQ and quercetin acted as inducers, but not the other compounds investigated. Reporter gene assays demonstrated that proximal promoter regions of the genes contribute to the induction by tBHQ, quercetin (MRP1) and clotrimazol (MRP2). However, the deletion of binding sites supposed to mediate the induction process (a PXR-binding element-like sequence for the clotrimazol effect and an ARE (antioxidative response element) for the tBHQ/quercetin effect) did not result in a significant decrease in the induction factor indicating that other parts of the promoter are probably involved in the induction process. In summary, expression of both genes can be up-regulated by redox-active compounds, while the other compounds tested induced only MRP2 but not MRP1 expression.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Kauffmann HM,Pfannschmidt S,Zöller H,Benz A,Vorderstemann B,Webster JI,Schrenk Ddoi
10.1016/s0300-483x(01)00570-4keywords:
subject
Has Abstractpub_date
2002-02-28 00:00:00pages
137-46issue
2-3eissn
0300-483Xissn
1879-3185pii
S0300483X01005704journal_volume
171pub_type
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