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

Donald Küfe(Dana-Farber Cancer Institute), Pierre Major(Dana-Farber Cancer Institute), E.Michael Egan(Dana-Farber Cancer Institute), G. Peter Beardsley(Dana-Farber Cancer Institute)
Journal of Biological Chemistry
October 1, 1980
10.1016/s0021-9258(19)70512-2
Cited by 362Open Access
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Abstract

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.

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