Experimental Studies with L-Asparaginase in Mouse Leukemias
The classic experimental studies of Kidd [1, 2], Broome [3–5], and others [6–14] in mice on the enzyme L-asparaginase (A-ase), originally as guinea pig serum and later as preparations of varying degrees of purity from E. coli, showed it to be a unique agent with a very high chemotherapeutic index which is capable of curing some mouse leukemias and tumors at high doses without assistance from host immune mechanisms. Since the drug also has a similar chemotherapeutic index in man [15–23], the metabolism and the mechanism of action of the drug in various strains of mouse leukemia and in patients with acute leukemia have been compared in an attempt to understand why — unlike in mouse leukemia — it has not so far been possible to produce regularly with this agent long-term unmaintained remissions in human acute leukemia. To this end, the dependence of various mouse and human cell lines on asparagine in vitro, the reversibility of the antileukemic effect of A-ase in vitro and in vivo, the effects of dose and dosage schedule on early and advanced ascitic, subcutaneous, and intracerebral leukemia, and the effect of prior or concomitant treatment with other chemotherapeutic agents on both the half-life of the drug and the increase in survival time of the leukemic animals have been investigated.
KeywordsAcute Lymphoblastic Leukemia Acute Leukemia Cytosine Arabinoside Vinca Alkaloid Nucleic Acid Synthesis
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