L-histidinol improves the selectivity and efficacy of alkylating agents and daunomycin in mice with P388 leukaemia.
DBA/2J mice bearing a clonal isolate of the transplantable murine lymphocytic leukaemia line P388 were used to examine the effects of L-histidinol on the antitumour activity of three alkalyating agents (bis-chloroethylnitrosourea (BCNU), cis-diamminedichloroplatinum (II) (cisDDP) and cyclophosphamide) and the antitumour antibiotic daunomycin. Single, combined treatments with L-histidinol and either BCNU or cisDDP, at doses of the alkylating agents which were ineffective when used alone, were completely curative. Dose-response studies showed that L-histidinol conferred dose-dependent, synergistic improvements on the capacities of both BCNU and cisDDP to increase the life-span of DBA/2J mice bearing P388 leukemia. For combinations of L-histidinol and cyclophosphamide or daunomycin, two successive treatments with L-histidinol and drug were required to obtain a significant portion of long-term survivors. Thus, in this model system, the L-histidinol/anticancer drug combination approach for improving experimental cancer chemotherapy can be employed successfully with three alkylating agents and the antitumour antibiotic daunomycin.
Warrington
R C
RC
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Fang
W D
WD
D000477:Alkylating Agents / Q000008:administration & dosage; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006641:Histidinol / Q000008:administration & dosage; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D008811:Mice, Inbred DBA
D000477:Alkylating Agents; D006641:Histidinol; D003520:Cyclophosphamide; D002945:Cisplatin; D002330:Carmustine; D003630:Daunorubicin