Combination therapy of mouse leukemia L1210 by 1-beta-D-arabinofuranosylcytosine and 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine.
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.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D003561:Cytarabine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D007288:Inosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D009578:Nitrobenzenes / Q000627:therapeutic use; D013440:Sulfides / Q000627:therapeutic use; D013868:Thioinosine / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D009578:Nitrobenzenes; D013440:Sulfides; D003561:Cytarabine; D013868:Thioinosine; D007288:Inosine; C001789:4-nitrobenzylthioinosine