Incorporation of 9-beta-D-arabinofuranosyl-2-fluoroadenine into HL-60 cellular RNA and DNA.
The incorporation of 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) into HL-60 cellular nucleic acids was monitored by cesium sulfate gradient centrifugation. The results demonstrated that F-ara-A incorporated into both RNA and DNA. These findings are in contrast to those previously obtained with 1-beta-D-arabinofuranosylcytosine (ara-C) and 9-beta-arabinofuranosyladenine (ara-A) which demonstrated incorporation of these nucleosides only in DNA. F-ara-A inhibited HL-60 proliferation, and the incorporation of F-ara-A into both DNA and RNA correlated with loss of clonogenic survival. Furthermore, cytostatic concentrations of F-ara-A resulted in the appearance of a more mature phenotype, a finding consistent with the effects of other inhibitors of DNA synthesis. The incorporation of F-ara-A into RNA and DNA should provide new insights regarding the mechanism of action of this agent.
D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D013997:Time Factors; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D014740:Vidarabine; C024352:fludarabine