Abstract
The antimetabolite 1-β-D-arabinofuranosylcytosine (ara-C) has proven to be one of the most effective agents available for the treatment of acute leukemia. While ara-C has been implicated as a potent inhibitor of mammalian cell DNA replication, the specific mechanism by which ara-C kills cells is not known. In this report we describe the development of an in vitro model system to study the molecular mechanism of ara-CMP incorporation into DNA. This model system makes use of a recently described human cell multiprotein DNA replication complex (MRC) that is competent to replicate DNA in vitro. The MRC can successfully incorporate ara-CMP into replicating DNA at internucleotide positions. These results are similar to those described for studies using intact cells. This MRC-driven in vitro replication system may therefore serve as a powerful model for the study of anticancer agents that directly affect human cell DNA synthesis.
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Received: 31 March 1995/Accepted: 9 October 1995
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Wills, P., Hickey, R., Ross, D. et al. A novel in vitro model system for studying the action of ara-C. Cancer Chemother Pharmacol 38, 366–372 (1996). https://doi.org/10.1007/s002800050496
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DOI: https://doi.org/10.1007/s002800050496