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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine Nucleotides / metabolism
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Aminoimidazole Carboxamide / analogs & derivatives*
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Aminoimidazole Carboxamide / pharmacology
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Cell Count
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Cell Death / drug effects
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Drug Interactions
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Guanine Nucleotides / metabolism
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Humans
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Mercaptopurine / analogs & derivatives*
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Mercaptopurine / antagonists & inhibitors*
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Methylthioinosine / analogs & derivatives
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Methylthioinosine / metabolism
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Ribonucleosides / pharmacology*
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Thioinosine / analogs & derivatives*
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Thionucleosides / antagonists & inhibitors*
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Thionucleotides / metabolism
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Time Factors
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Tumor Cells, Cultured / drug effects*
Substances
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Adenine Nucleotides
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Guanine Nucleotides
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Ribonucleosides
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Thionucleosides
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Thionucleotides
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Methylthioinosine
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Aminoimidazole Carboxamide
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Thioinosine
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acadesine
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6-methylthiopurine ribonucleoside-5'-phosphate
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Mercaptopurine