PT  - JOURNAL ARTICLE
AU  - D W Kufe
AU  - D Munroe
AU  - D Herrick
AU  - E Egan
AU  - D Spriggs
TI  - Effects of 1-beta-D-arabinofuranosylcytosine incorporation on eukaryotic DNA template function.
DP  - 1984 Jul 01
TA  - Molecular Pharmacology
PG  - 128--134
VI  - 26
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/26/1/128.short
4100  - http://molpharm.aspetjournals.org/content/26/1/128.full
SO  - Mol Pharmacol1984 Jul 01; 26
AB  - 1-beta-D-Arabinofuranosylcytosine (ara-C) 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. The present studies confirm that incorporation of ara-C into DNA, and not the competitive inhibition of DNA polymerase, is responsible for inducing lethal cellular events. The results also demonstrate that the incorporated ara-C residue is not excised from the DNA strand. Furthermore, the presistence 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.