Correlation of cytotoxicity with incorporation of ara-C into DNA.

We have employed cesium sulfate density gradient analysis to monitor the incorporation of 1-beta-D-arabinofuranosylcytosine (ara-C) into L1210 cellular nucleic acid. This methodology permits a distinct separation of RNA and DNA under nondegrading conditions. The results demonstrate specific incorporation of ara-C into DNA with less than 1% of total incorporation into nucleic acid being detectable in RNA. Moreover, we have found a highly significant relationship (p < 0.0001) between the incorporation of ara-C into DNA with the loss of clonogenic survival. This relationship had not been established due to the previous use of alkaline conditions that degrade (ara-C) DNA. Our results suggest that the incorporation of ara-C into DNA is one mechanism responsible for producing lethal cellular events.