In vivo efficacy of HAT therapy against transplantable murine myelomas resistant to purine analogs.
The therapeutic efficacy of antineoplastic purine analogs can be jeopardized by the emergence of drug-resistant mutant subpopulations of tumor cells. To determine whether such mutant populations might be eradicable in vivo with the type of HAT combination (hypoxanthine + an antifolate + thymidine) known to be selectively cytotoxic to them in vitro, 2 thioguanine-resistant BALB/c murine myeloma lines were transplanted into BALB/c mice to produce tumors capable of progressive growth in the absence of therapy. Treatment of these mice with a modified HAT regimen induced permanent tumor regressions in 37/44 mice; the same treatment was ineffective against tumors produced by a non-mutant myeloma line from which one of the mutant sublines had been derived.
D000630:Aminopterin / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004351:Drug Resistance; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010954:Plasmacytoma / Q000188:drug therapy*; D013866:Thioguanine / Q000627:therapeutic use*; D013936:Thymidine / Q000008:administration & dosage / Q000627:therapeutic use
D007042:Hypoxanthines; D019271:Hypoxanthine; D013866:Thioguanine; D000630:Aminopterin; D013936:Thymidine