SELECTION AND PARTIAL CHARACTERIZATION OF CALCIUM IONOPHORE (A23187) RESISTANT CELLS

We have selected calcium ionophore (A23187)-resistant cells (AR-7) in a human promyelocytic leukemia cell line, HL-60. AR-7 showed approxima tely 8.5-fold resistance to A23187 compared with the wild type cells a fter continuous exposure for 3 days. AR-7 had cross resistance to iono mycin (4.6-fold) and thapsigargin (340-fold) which can also increase i ntracellular Ca++. Similar magnitude of resistance to apoptosis, as de fined by characteristic morphology and internucleosomal DNA fragmentat ion, induced by these agents was observed after 4 hr of incubation. Ho wever, both the elevation of intracellular Ca++ following stimulation with various concentrations of A23187 and the sensitivity to anticance r agents including etoposide, 1-beta-D arabinofuranosylcytosine, and h ydroxyurea were comparable between the two cell types. This cell line is considered to be useful for exploring the mechanism(s) of cell deat h, especially apoptosis, induced by calcium ionophore. (C) 1995 academ ic Press, Inc.