DNA strand breaks caused by inhibitors of DNA synthesis: 1-beta-D-arabinofuranosylcytosine and aphidicolin.

Abstract

We have used alkaline elution analysis to determine whether strand breaks are detectable in L1210 DNA labeled during and prior to 1-beta-D-arabinofuranosylcytosine (ara-C) exposure. The results demonstrate that ara-C enhances elution of previously synthesized DNA as well as replicating DNA. ara-C induced dose-dependent strand breaks when DNA was labeled prior to drug exposure. In contrast, simultaneous exposure of cells to tritiated thymidine and drug resulted in maximal elution rates with 10(-6) M ara-C. These findings are compared to those obtained with aphidicolin, another inhibitor of DNA synthesis, which unlike ara-C is not incorporated into the DNA strand. These results suggest that both ara-C and aphidicolin increase DNA elution rates by impairing DNA synthesis. The different dose-dependent patterns during replicative DNA synthesis may result from the incorporation of ara-C in the DNA strand.