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Augmentation of Therapeutic Efficacy of 3',5'-Dichloroamethopterin against an Antifolic-resistant Variant of Leukemia (L1210-M46R) in Mice

( Laboratory of Chemical Pharmacology, National Cancer Institute, Bethesda, Maryland)

Augmentation of the therapeutic effectiveness of 3',5'-dichloroamethopterin (DCM) against the M46R resistant variant of leukemia L1210 was demonstrated in mice preinoculated with the sensitive line of leukemia L1210. The increases in survival time were almost as extensive as those observed on treatment of the sensitive leukemia L1210 alone.

The augmentation of therapy for the M46R resistant variant in L1210-pretreated mice appeared to be dependent upon a schedule of continuous therapy.

In experiments in which the sensitive leukemia and the M46R resistant variant were inoculated concomitantly, no augmentation of therapy was obtained.

The employment of resistant sublines of tumor as tools in the study of the interrelationships of host-tumor factors in chemotherapy is discussed.

With the Technical Assistance of Gerome McDowell

Received 1/13/60.