COMBINED CYTOSINE-ARABINOSIDE PLUS INTERFERON-ALPHA .1. INTERFERON-ALPHA POTENTIATES THE EFFECT OF CYTOSINE-ARABINOSIDE IN HL-60 CELLS BY STIMULATION OF APOPTOSIS

: Incubation of HL 60 human leukemia cells with cytosine arabinoside resulted in a dose and time dependant increase of cytotoxicity. The characteristics of the mechanism of cytotoxicity were shown to correspond to those of apoptotic cell death. Addition of interferon alpha in amounts as low as 10 u/ml potentiated the apoptosis inducing effect of cytosine arabinoside and moreover prevented recovery from sublethal toxicity after short duration exposure to the latter drug. The role of apoptosis as a mechanism for the lethal effects of certain cytotoxic agents is discussed. Perturbations of a number of different metabolic pathways appear to be able to trigger apoptosis-like cell death depending on, among other factors, cell lineage. While the HL 60 in vitro model may be particularly sensitive to apoptotic cell death by virtue of increased c-myc expression this propensity may well make it a suitable model for the development of clinical treatment regimens for patients with a number of hematologic malignancies which are characterized by increased c-myc expression in vivo.