Relationship between incorporation of 9-beta-D-arabinofuranosyladenine in L 1210 DNA and cytotoxicity.

We have used cesium sulfate density gradient centrifugation to monitor the incorporation of 9-beta-D-arabinofuranosyladenine (ara-A) into L1210 cellular nucleic acids. The results demonstrate the specific incorporation of ara-A in L1210 DNA. We have also found a highly significant relationship between the formation of ara-A incorporated into DNA and loss of clonogenic survival. This relationship was maintained when using ara-A in the presence of the adenosine deaminase inhibitor deoxycoformycin. Furthermore, treatment with increasing concentrations of ara-A resulted in a greater proportion of ara-A residues at the 3'-terminus, consistent with this agent providing a poor primer terminus for elongating DNA strands. These findings are similar to those obtained previously with 1-beta-D-arabinofuranosylcytosine and suggest that the incorporation of arabinofuranosyl derivatives in DNA is one mechanism responsible for cell lethality.