Abstract
We have used cesium sulfate density gradient centrifugation to monitor the incorporation of 9-β-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-β-d-arabinofuranosylcytosine and suggest that the incorporation of arabinofuranosyl derivatives in DNA is one mechanism responsible for cell lethality.
Footnotes
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↵1 This work was supported by Grant No. CH-199 from the American Cancer Society.
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↵2 Recipient of an American Cancer Society Faculty Research Award. To whom requests for reprints should be addressed at Sidney Farber Cancer Institute, 44 Binney Street, Boston, Mass., 02115.
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↵3 Recipient of a fellowship from the Medical Research Council of Canada.
- Received August 11, 1982.
- Accepted February 1, 1983.
- ©1983 American Association for Cancer Research.
Volume 43, Issue 5
