A novel in vitro model system for studying the action of ara-C.

Abstract:

:The antimetabolite 1-beta-D-arabinofuranosyl-cytosine (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.

authors

Wills P,Hickey R,Ross D,Cuddy D,Malkas L

doi

10.1007/s002800050496

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

366-72

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

38

pub_type

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