Effect of ARA-C incorporation on deoxyribonucleic acid synthesis in cells

Recent work using isolated DNA polymerase-template complexes has shown that arabinofuranosyl derivatives con slow DNA synthesis by being incorporated into DNA. Our results suggest that these agents act by a similar mechanism in L1210 cells. The results demonstrate that inhibition of cellular DNA synthesis by cytosine arabinoside (ara-C) was significantly related to the extent of ara-C incorporation in DNA over a wide range of drug concentrations and times of exposure. Furthermore, treatment with increasing concentrations of ara-C resulted in a greater proportion of ara-C residues at the 3'-terminus of the elongating DNA chain. These observations suggest that ara-C incorporation results in poor primer termini for further chain elongation.