Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrobenzylthioinosine (NBMPR), an inhibitor of nucleoside transport, was tested in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) for therapeutic activity against mouse leukemia L1210. NBMPR alone had no activity, whereas therapy with NBMPR and ara-C in combination was significantly better than with ara-C alone. The therapeutic potentiation resulting from the combination of NBMPR and ara-C appeared to be host mediated since NBMPR alone was not toxic to cultured L1210 cells. NBMPR treatment of normal mice increased the plasma half-time of ara-C and decreased rates of urinary excretion of ara-C and 2'-deoxycytidine; however, these effects were not large enough to explain the therapeutic potentiation. Because the drug combination appeared to be no more effective than ara-C alone in therapy of mouse leukemia L1210/TG (a thiopurine-resistant L1210 subline lacking hyposanthine-guanine phosphoribosyltransferase), the host-mediated therapeutic potentiation was attributed in in vivo breakdown of NBMPR to 6-mercaptopurine.
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PMID:Combination therapy of mouse leukemia L1210 by 1-beta-D-arabinofuranosylcytosine and 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine. 112 Mar 8

9-beta-D-Arabinofuranosyl-2-fluoroadenine (F-ara-A) and 9-beta-D-arabinofuranosyladenine (ara-A) are purine nucleoside analogues which are incorporated into nucleic acids. This study demonstrates the mutagenic properties of F-ara-A and ara-A and provides evidence for mechanisms by which the arabinosyl nucleosides induce mutation. At the drug dosages that evoked exponential cell killing, F-ara-A and ara-A caused a significant increase in the number of 6-thioguanine-resistant mutants in Chinese hamster ovary cells. Southern analyses showed that 15 of 16 drug-induced mutants had lost all or part of the HPRT gene, whereas no loss of the gene was found in 4 spontaneous mutants. We conclude that both F-ara-A and ara-A induced mutation predominantly by causing deletion of genetic material. The remarkable frequency of gene deletion among these drug-induced mutations is discussed with respect to possible mechanisms of action of arabinosyl nucleosides in mutational studies.
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PMID:Gene deletion, a mechanism of induced mutation by arabinosyl nucleosides. 291 Dec 56