title: A novel bioluminescent bacterial biosensor for measurement of Ara-CTP and cytarabine potentiation by fludarabine in seven leukaemic cell lines.
abstract: This study evaluates an in vitro biosensor assay capable of detecting the intracellular levels of the tri-phosphorylated form of cytarabine (Ara-CTP) within one working day. The biosensor predicted the response of seven leukaemic cell lines with varying known sensitivities to cytarabine alone and in combination with fludarabine. High-performance liquid chromatography (HPLC), 3-day assessment of cellular viable mass, and flow cytometric assessment of apoptosis were used to validate biosensor performance. A correlation between the biosensor results and Ara-CTP quantitation by HPLC was confirmed (R=0.972). The biosensor was also capable of detecting enhanced accumulation of Ara-CTP following sequential pre-treatment of leukaemic cells with cytarabine ± fludarabine.
authors.affiliation: Centre for Research in Biosciences, Faculty of Health and Life Sciences, University of the West of England, Bristol BS16 1QY, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Anderson
authors.forename: M Ann
authors.initials: MA
authors.lastname: Smith
authors.forename: Ashley
authors.initials: A
authors.lastname: Martin
authors.forename: Mark
authors.initials: M
authors.lastname: Ruddock
authors.forename: John
authors.initials: J
authors.lastname: Lamont
authors.forename: Habib
authors.initials: H
authors.lastname: Alloush
authors.forename: Myra
authors.initials: M
authors.lastname: Conway
authors.forename: Priyanka
authors.initials: P
authors.lastname: Mehta
authors.forename: J Graham
authors.initials: JG
authors.lastname: Smith
authors.forename: Vyv
authors.initials: V
authors.lastname: Salisbury
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001085:Arabinofuranosylcytosine Triphosphate / Q000032:analysis*; D001426:Bacterial Proteins / Q000032:analysis; D015374:Biosensing Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D008163:Luminescent Measurements / Q000379:methods; D008164:Luminescent Proteins / Q000032:analysis; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate; D014740:Vidarabine; C024352:fludarabine