Correlation of cytotoxicity with incorporation of ara-C into DNA.
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.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000378:metabolism / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D007700:Kinetics; D007939:Leukemia L1210 / Q000503:physiopathology*; D051379:Mice
D004273:DNA, Neoplasm; D003561:Cytarabine