APHIDICOLIN POTENTIATES APOPTOSIS INDUCED BY ARABINOSYL NUCLEOSIDES IN HUMAN MYELOID-LEUKEMIA CELL-LINES

We investigated the effect of aphidicolin, an inhibitor of DNA polymer ase alpha and delta, on the induction of apoptosis by arabinosyl nucle osides in a human promyelocytic leukemia cell line, HL-60. Pretreatmen t of HL-60 cells with aphidicolin (2 mu M) significantly increased the number of morphologically apoptotic cells induced by 1-beta-D arabino furanosylcytosine (ara-C) during 4 hr of incubation. This is consisten t with the appearance of DNA fragmentation as determined quantitativel y by diphenylamine or by agarose gel electrophoresis. The inhibition o f cell growth on day 3 after drug exposure was correlated with the deg ree of apoptosis. Such synergistic interaction between aphidicolin and ara-C has also been observed in other human myeloid leukemia cell lin es, U937 and KG-1. In addition, the induction of apoptosis by 9-beta-D arabinofuranosyladenine or 9-beta-D arabinofuranosylguanine is augmen ted by aphidicolin.