EFFECTS OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE INCORPORATION ON EUKARYOTIC DNA-TEMPLATE FUNCTION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 26  (1) , 128-134
Abstract
1-.beta.-D-Arabinofuranosylcytosine (ara-C) [the most effective agent in the treatment of a human acute myelogenous leukemia] incorporates into DNA, and the extent of this incorporation correlates significantly with inhibition of DNA synthesis. The incorporated ara-C residue provides a poor primer terminus for further chain elongation. There is a highly significant relationship between formation of (ara-C)DNA and loss of clonogenic survival. Incorporation of ara-C into DNA, and not the competitive inhibition of DNA polymerase, is responsible for inducing lethal cellular events. The incorporated ara-C residue is not excised from the DNA strand. The persistence of ara-C residues in DNA inhibits recovery of DNA synthesis following exposure to drug. The relative DNA chain-terminating effect of ara-C provides several mechanisms of action that explain internucleotide and chain terminus positioning of ara-C residues, reinitiation of previously replicated DNA segments, and DNA strand or chromosomal breaks. The precise mechanism of action is dependent upon dose scheduling of this drug.