Abstract
We investigate the effect of aphidicolin, an inhibitor of DNA polymerase α and δ, on the induction of apoptosis by arabinosyl nucleotides in a human promyelocytic leukemia cell line, HL-60. Pretreatment of HL-60 cells with aphidicolin (2μM) significantly increased the number of morphologically apoptotic cells induced by 1-β- D arabinofuranosylcytosine (ara-C) during 4 hr of incubation. This is consistent with the appearance of DNA fragmentation as determined quantitatively by diphenylamine or by agarose gel electrophoresis. The inhibition of cell growth on day 3 after drug exposure was correlated with the degree of apoptosis. Such synergistic interaction between aphidicolin nd ara-C has also been observed in other human myeloid leukemia cell lines, U937 and KG-1. In addition, the induction of apoptosis by 9-β- D arabinofuranosyladenine or 9-β- D arabinofuranosylguanine is augmented by aphidicolin.
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