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Reduction in the Frequency of Mutation to Resistance to Cytarabine in L1210 Murine Leukemic Cells by Treatment with Quinacrine Hydrochloride

The Upjohn Company, Research Division, Kalamazoo, Michigan 49001

The cloning of single cells in agar was employed to study the effect of the addition of quinacrine hydrochloride to cultures of L1210 cells on the frequency of the mutation to resistance to cytarabine (ara-C). In three independent experiments this frequency was reduced 5-to 16-fold after prolonged culture in the presence of quinacrine. Attempts to demonstrate a concomitant increase in the number of L1210-bearing leukemic mice which are "cured" by combining ara-C treatments with treatments with quinacrine under idealized experimental conditions yielded marginally significant results in the predicted direction. The results can be interpreted as supporting an antimutagenic effect of quinacrine on mammalian cells similar to the antimutagenic effect of this compound in bacterial cells which we had demonstrated previously.

Received 12/16/68. Accepted 6/25/69.