Lethality of human myeloblasts correlates with the incorporation of arabinofuranosylcytosine into DNA.

We recently demonstrated a highly significant relationship between the incorporation of 1-beta-D-arabinofuranosylcytosine (ara-C) into L1210 DNA and the loss of clonogenic survival. These studies have now been extended to the human promyeloblast (HL-60) cell line and myeloblasts from a patient with acute myelogenous leukemia. Our results demonstrate: (i) the specific internucleotide incorporation of ara-C into human myeloblast DNA; (ii) the lability of [3H]ara-C-labeled DNA to alkali which necessitates the use of nondegrading assay conditions; and (iii) a highly significant relationship (P less than 0.0001) between the loss of clonogenicity of these cells and the extent of ara-C incorporation. These findings suggest that the incorporation of ara-C into DNA is one of the initial events leading to cell lethality. This method is applicable to clinical samples of bone marrow and peripheral blood as an in vitro assay for studying the sensitivity of cell populations to this drug.