Up-regulation of transporters of the MRP family by drugs and toxins

Expression of a variety of ABC efflux pumps including certain conjugate tra nsporters of the multidrug resistance protein (MRP) subfamily is inducible in primate and rodent tissues, and in a variety of cell lines and primary c ells in culture. In human cell lines (HepG2, MCF-7), we studied the inducib ility of MRPs 1-5. Similar to the rat mrp2 gene, human, mrp2 is inducible b y the chemical carcinogen 2-AAF, the chemotherapeutic drug cisplatin and th e barbiturate phenobarbital. as demonstrated in Northern and Western Blots. Furthermore, the antibiotic rifampicin was identified as MRP2 inducer in H epG2 cells. MRP1 and 4 mRNAs being expressed in human liver at a very low l evel could not be detected in HepG2 cells after treatment with various agen ts. However, MRP3 and 5 mRNAs were detected in addition to MRP2 and their e xpression was found to be increased by 2-AAF, cisplatin and rifampicin. MRP I expression was studied in MCF-7 cells where the chemotherapeutic drug vin blastine and tert-butyl hydroquinone but not the MRP2 inducing agents descr ibed above acted as inducers. (C) 2001 Elsevier Science ireland Ltd. All li ghts reserved.