title: Incorporation of N4-behenoyl-1-beta-D-arabinofuranosylcytosine into DNA as 1-beta-D-arabinofuranosylcytosine.
abstract: BHAC is a newly synthesized lipophilic derivative of ara-C. To clarify its pharmacological mode of action, P388 murine leukemic cells were incubated with two different types of 14C-labeled BHAC, [cytosine-2-14C]BHAC and [acyl-1-14C]BHAC, and DNA was extracted with phenol. The phenol-extracted DNA was then hydrolyzed by nuclease P1 and analyzed with high-performance liquid chromatography (HPLC). The radioactivity of DNA, from the cells incubated with [cytosine-2-14C]BHAC, was detected as ara-CMP. But the radioactivity of DNA, from the cells incubated with [acyl-1-14C]BHAC, was hardly detected. On the other hand, the main radioactivity of the acid soluble fraction was determined as ara-CTP. On the basis of our results, BHAC is not phosphorylated directly to produce N4-behenoyl-ara-CTP, but is mainly converted to ara-C which subsequently produces ara-CTP, the active metabolite of the drug, and which is then incorporated into DNA.
authors.affiliation: Department of Pediatrics, Mie University School of Medicine, Tsu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Higashigawa
authors.forename: H
authors.initials: H
authors.lastname: Ochiai
authors.forename: T
authors.initials: T
authors.lastname: Ohkubo
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: T
authors.initials: T
authors.lastname: Nobori
authors.forename: H
authors.initials: H
authors.lastname: Kamiya
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D006868:Hydrolysis; D051379:Mice; D009708:Nucleotidases / Q000378:metabolism; D019800:Phenol; D010636:Phenols; D012588:Scintillation Counting; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010636:Phenols; D003561:Cytarabine; D019800:Phenol; D004247:DNA; C015019:enocitabine; D009708:Nucleotidases; D015719:Single-Strand Specific DNA and RNA Endonucleases