L-Histidinol improves the selectivity and efficacy of alkylating agents and daunomycin in mice with P388 leukaemia

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Abstract
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.