title: Reversal of 6-mercaptopurine and 6-methylmercaptopurine ribonucleoside cytotoxicity by amidoimidazole carboxamide ribonucleoside in Molt F4 human malignant T-lymphoblasts.
abstract: Cytotoxicity of 6-mercaptopurine (6MP) and 6-methylmercaptopurine ribonucleoside (Me-MPR) was studied in Molt F4 human malignant lymphoblasts. Both drugs are converted into methylthioIMP (Me-tIMP), which inhibits purine de novo synthesis. Addition of amidoimidazole carboxamide ribonucleoside (AICAR) circumvented inhibition of purine de novo synthesis, and thus partly prevented 6MP and Me-MPR cytotoxicity. Purine nucleotides, and especially adenine nucleotides, were recovered by addition of AICAR. Under these conditions, Me-tIMP formation decreased. The results of this study indicate that formation of Me-tIMP may be important for 6MP cytotoxicity in Molt F4 cells. These data suggest that depletion of adenine nucleotides is the main cause for Me-tIMP cytotoxicity.
authors.affiliation: Department of Pediatrics, St. Radboud University Hospital of Nijmegen, The Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: Stet
authors.forename: R A
authors.initials: RA
authors.lastname: De Abreu
authors.forename: J P
authors.initials: JP
authors.lastname: Bökkerink
authors.forename: T M
authors.initials: TM
authors.lastname: Vogels-Mentink
authors.forename: L H
authors.initials: LH
authors.lastname: Lambooy
authors.forename: F J
authors.initials: FJ
authors.lastname: Trijbels
authors.forename: R C
authors.initials: RC
authors.lastname: Trueworthy
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004347:Drug Interactions; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D008778:Methylthioinosine / Q000031:analogs & derivatives / Q000378:metabolism; D012263:Ribonucleosides / Q000494:pharmacology*; D013868:Thioinosine / Q000031:analogs & derivatives*; D013872:Thionucleosides / Q000037:antagonists & inhibitors*; D013873:Thionucleotides / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000227:Adenine Nucleotides; D006150:Guanine Nucleotides; D012263:Ribonucleosides; D013872:Thionucleosides; D013873:Thionucleotides; D008778:Methylthioinosine; D000620:Aminoimidazole Carboxamide; D013868:Thioinosine; C011651:acadesine; C002344:6-methylthiopurine ribonucleoside-5'-phosphate; D015122:Mercaptopurine