Thiopurine metabolism and identification of the thiopurine metabolites transported by MRP4 and MRP5 overexpressed in human embryonic kidney cells

Molecular Pharmacology

Volumn 62, Issue 6, 2002, Pages 1321-1331

  Wielinga, P R ^a   Reid, G ^a   Challa, E E ^b   Van Der Heijden, I ^a   Van Deemter, L ^a   De Haas, M ^a   Mol, C ^a   Kuil, A J ^a   Groeneveld, E ^a   Schuetz, J D ^c   Brouwer, C ^d   De Abreu, R A ^d   Wijnholds, J ^a   Beijnen, J H ^b   Borst, P ^a  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b SLOTERVAART HOSPITAL   (Netherlands)

^c ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE; ANTINEOPLASTIC AGENT; MERCAPTOPURINE; MERCAPTOPURINE RIBOSIDE; MULTIDRUG RESISTANCE PROTEIN; THIOXANTHINE; TIOGUANINE; UNCLASSIFIED DRUG;

ARTICLE; DRUG TRANSPORT; EMBRYO; ENZYME PHOSPHORYLATION; ENZYME SPECIFICITY; ENZYME SUBSTRATE; GENE OVEREXPRESSION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IMMUNOBLOTTING; KIDNEY CELL; MULTIDRUG RESISTANCE; PRIORITY JOURNAL; PURINE METABOLISM;

6-MERCAPTOPURINE; BIOLOGICAL TRANSPORT; CELLS, CULTURED; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG INTERACTIONS; HUMANS; KIDNEY; KINETICS; METHYLTHIOINOSINE; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; RIBOSOMAL PROTEINS; THIOGUANINE; TRANSFECTION;

EID: 0036893815     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: 10.1124/mol.62.6.1321     Document Type: Article

References (40)

1. Adachi M, Sampath J, Lan L-B, Sun D, Hargrove P, Flatley RM, Tatum A, Ziegelmeier MZ, Wezeman M, Matherly LH, et al. (2002) Expression of MRP4 confers resistance to ganciclovir and compromises bystander cell killing. J Biol Chem 277:38998-39004.
2. Aubrecht J, Goad ME, and Schiestl RH (1997) Tissue specific toxicities of the anticancer drug 6-thioguanine is dependent on the Hprt status in transgenic mice. J Pharmacol Exp Ther 282:1102-1108.
3. Baldwin SA, Mackey JR, Cass CE, and Young JD (1999) Nucleoside transporters: Molecular biology and implications for therapeutic development. Mol Med Today 5:216-224.
4. Belinsky MG, Bain LJ, Balsara BB, Testa JR, and Kruh GD (1998) Characterization of MOAT-C and MOAT-D, new members of the MRP/CMOAT subfamily of transporter proteins. J Natl Cancer Inst 90:1735-1741.
5. Bera TK, Lee S, Salvatore G, Lee B, and Pastan I (2001) MRP8, a New Member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer. Mol Med 7:509-516.
6. Borst P, Evers R, Kool M, and Wijnholds J (2000) A family of drug transporters: The multidrug resistance-associated proteins. J Natl Cancer Inst 92:1295-1302.
7. Breter HJ and Mertes H (1990) The quantitative determination of metabolites of 6-mercaptopurine in biological materials. VII. Chemical synthesis by phosphorylation of 6-thioguanosine 5′-monophosphate, 5′-diphosphate and 5'-triphosphate and their purification and identification by reversed-phase/ion -pair high-performance liquid chromatography and by various enzymatic assays. Biochim Biophys Acta 1033:124-132.
8. Burchenal JH, Murphy ML, and Ellison RR (1953) Clinical evaluation of a new antimetabolite, 6-mercaptopurine, in the treatment of acute leukemia and allied diseases. Blood 8:965-999.
9. Chen ZS, Lee K, and Kruh GD (2001) Transport of cyclic nucleotides and estradiol 17-β-D-glucuronide by multidrug resistance protein 4: Resistance to 6-mercaptopurine and 6-thioguanine. J Biol Chem 276:33747-33754.
10. Elion GB (1989) The purine path to chemotherapy. Science (Wash DC) 244:41-47.
11. Elion GB, Burgi E, and Hitchings GH (1952) Studies on condensed pyrimidine systems: IX. The synthesis of some 6-substituted purines. J Am Chem Soc 74:411-414.
12. Harlow E and Lane D (1988) Antibodies: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
13. Hipfner DR, Deeley RG, and Cole SP (1999) Structural, mechanistic and clinical aspects of MRP1. Biochim Biophys Acta 1461:359-376.
14. Hunsucker SA, Spychala J, and Mitchell BS (2001) Human cytosolic 5′-nucleotidase I: Characterization and role in nucleoside analog resistance. J Biol Chem 276: 10498-10504.
15. Jedlitschky G, Burchell B, and Keppler D (2000) The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J Biol Chem 275:30069-30074.
16. Keuzenkamp-Jansen CW, De Abreu RA, Bokkerink JP, and Trijbels JM (1995) Determination of extracellular and intracellular thiopurines and methylthiopurines by high-performance liquid chromatography. J Chromatogr B Biomed Appl 672:53-61.
17. Kool M, de Haas M, Scheffer GL, Scheper RJ, van Eijk MJ, Juijn JA, Baas F, and Borst P (1997) Analysis of expression of CMOAT (MRP2), MRP3, MRP4 and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res 57:3537-3547.
18. Krynetski EY, Schuetz JD, Galpin AJ, Pui CH, Relling MV, and Evans WE (1995) A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc Natl Acad Sci USA 92:949-953.
19. Lee K, Klein-Szanto AJ, and Kruh GD (2000) Analysis of the MRP4 drug resistance profile in transfected NIH3T3 cells. J Natl Cancer Inst 92:1934-1940.
20. Lennard L, Van Loon JA, Lilleyman JS, and Weinshilboum RM (1987) Thiopurine pharmacogenetics in leukemia: Correlation of erythrocyte thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations. Clin Pharmacol Ther 41:18-25.
21. LePage GA (1963) Basic biochemical effects and mechanism of action of 6-thioguanine. Cancer Res 23:1202-1206.
22. Lilleyman JS and Lennard L (1994) Mercaptopurine metabolism and risk of relapse in childhood lymphoblastic leukaemia. Lancet 343:1188-1190.
23. Lowe ES, Kitchen BJ, Erdmann G, Stork LC, Bostrom BC, Hutchinson R, Holcenberg J, Reaman GH, Woods W, Franklin J, et al. (2001) Plasma pharmacokinetics and cerebrospinal fluid penetration of thioguanine in children with acute lymphoblastic leukemia: A collaborative Pediatric Oncology Branch, NCI and Children's Cancer Group Study. Cancer Chemother Pharmacol 47:199-205.
24. Markowitz J, Grancher K, Kohn N, Lesser M, and Daum F (2000) A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology 119:895-902.
25. Martin DS (1987) Purine and pyrimidine biochemistry and some relavant clinical and preclinical cancer chemotherapy research, in Metabolism and Action of Anti-Cancer Drugs (Powis G and Prough AR eds) pp 91-139, Taylor and Francis, London.
26. McAleer MA, Breen MA, White NL, and Matthews N (1999) PABC11 (also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confer multidrug resistance when overexpressed in human embryonic kidney 293 cells. J Biol Chem 274:23541-23548.
27. Pieters R, Huismans DR, Loonen AH, Peters GJ, Hahlen K, van der Does-van den Berg, van Wering ER, and Veerman AJ (1992) Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia. Leuk Res 16:873-880.
28. Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui CH, and Evans WE (1999) Mercaptopurine Therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 91:2001-2008.
29. Rosman M, Lee MH, Creasey WA, and Sartorelli AC (1974) Mechanisms of resistance to 6-thiopurines in human leukemia. Cancer Res 34:1952-1956.
30. Schuetz JD, Connelly MC, Sun D, Paibir SG, Flynn PM, Srinivas RV, Kumar A, and Fridland A (1999) MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nat Med 5:1048-1051.
31. Skladanowski AC, Hoffmann C, Krass J, Jastorff B, and Makarewicz W (1996) Structure-activity relationship of cytoplasmic 5′-nucleotidase substrate sites. Biochem J 314:1001-1007.
32. Versantvoort CH, Broxterman HJ, Bagrij T, Scheper RJ, and Twentyman PR (1995) Regulation by glutathione of drug transport in multidrug-resistant human lung tumour cell lines overexpressing multidrug resistance-associated protein. Br J Cancer 72:82-89.
33. Tammur J, Prades C, Arnould I, Rzhetsky A, Hutchinson A, Adachi M, Schuetz JD, Swoboda KJ, Ptacek LJ, Rosier M, et al. (2001) Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12. Gene 273:89-96.
34. van Aubel RA, Smeets PH, Peters JG, Bindels RJ, and Russel FG (2002) The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubule: The putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol 13:595-603.
35. Vogt MH, Stet EH, De Abreu RA, Bokkerink JP, Lambooy LH, and Trijbels FJ (1993) The importance of methylthio-IMP for methylmercaptopurine ribonucleoside (Me-MPR) cytotoxicity in Molt F4 human malignant T-lymphoblasts. Biochim Biophys Acta 1181:189-194.
36. Wijnholds J, Mol CA, van Deemter L, de Haas M, Scheffer GL, Baas F, Beijnen JH, Scheper RJ, Hatse S, De Clercq E, et al. (2000) Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc Natl Acad Sci USA 97:7476-7481.
37. Yabuuchi H, Shimizu H, Takayanagi S, and Ishikawa T (2001) Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12. Biochem Biophys Res Commun 288:933-939.
38. Zaman GJ, Lankelma J, van Tellingen O, Beijnen J, Dekker H, Paulusma C, Oude Elferink RP, Baas F, and Borst P (1995) Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein. Proc Natl Acad Sci USA 92:7690-7694.
39. Zimm S, Johnson GE, Chabner BA, and Poplack DG (1985) Cellular pharmacokinetics of mercaptopurine in human neoplastic cells and cell lines. Cancer Res 45:4156-4161.
40. Zimm S, Reaman G, Murphy RF, and Poplack DG (1986) Biochemical parameters of mercaptopurine activity in patients with acute lymphoblastic leukemia. Cancer Res 46:1495-1498.