Combinational chemotherapy of L1210 and L1210/ARA-C leukemia with 5-AZA-2'-deoxycytidine and beta-2'-deoxythioguanosine.
The in vitro and in vivo antineoplastic activity of 5-AZA-2'-deoxycytidine (5-AZA-CdR) and beta-2'-deoxythioguanosine (TGdR) on L1210 and L1210/ARA-C (resistant to cytosine arabinoside) leukemic cells was investigated. 5-AZA-CdR was a very potent cytotoxic agent against the L1210 leukemia cells. This analogue was inactive against L1210/ARA-C leukemic cells because these cells lack deoxycytidine kinase, the enzyme that converts 5-AZA-CdR to its active nucleotide form. TGdR was a potent cytotoxic agent to both L1210 and L1210/ARA-C leukemic cells. In mice which were injected simultaneously with both L1210 and L1210/ARA-C leukemic cells, the drug combination of 5-AZA-CdR plus TGdR had a very potent antineoplastic activity and produced long-term survivors. Either agent alone did not produce any long-term survivors in the mice with L1210 and L1210/ARA-C leukemia. This experimental model indicates that 5-AZA-CdR plus TGdR is an interesting drug combination for the treatment of leukemia with drug-resistant cells.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077209:Decitabine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D007939:Leukemia L1210 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D013872:Thionucleosides / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D013872:Thionucleosides; D000077209:Decitabine; C010438:beta-2'-deoxythioguanosine; D003849:Deoxyguanosine; D001374:Azacitidine