Mechanism of action of 1-beta-D-arabinofuranosyl-5-azacytosine and its effects in L1210 mouse leukemia cells.

Ara-5AC depresses the growth of L1210 cells in vivo in a manner that is schedule-independent and at the dose levels which are similar to those of ara-C. The 50% inhibitory concentration for ara-5AC in L1210 system is about 0.75 microM. In distinction to ara-C the drug does not elicit the proliferation of proerythroblasts in the mouse bone marrow. It is phosphorylated by dCyd kinase, and the respective Km value is 70 microM. Ara-5AC is incorporated into DNA and almost completely blocks the incorporation of thymidine at a concentration of 10 microM.