Disease relevance of Ara-U

• By contrast, 1-beta-D-arabinofuranosyluracil predominated in hydrolysates of monophosphate nucleotide fractions from ascites cells, liver, small intestine, and blood [1].
• Inhibition of deoxyribonucleic acid polymerases from murine cells and oncornavirus by 5-alkylated derivatives of 1-beta-D-arabinofuranosyluracil 5'-triphosphate: substituent effects on inhibitory action [2].
• A number of antiherpesviral 5-substituted derivatives of 1-beta-D-arabinofuranosyluracil (araU) were significantly resistant to phosphorolysis by rat liver extract (S-9), but were gradually deglycosylated in a 2% enterobacteria cell suspension [3].
• In vivo studies on high-dose 1-beta-D-arabinofuranosylcytosine (HDara-C) and 1-beta-D-arabinofuranosyluracil (ara-U) with respect to pharmacokinetics, cell kinetics, and cytotoxicity in a rat myelocytic leukemia model (BNML) [4].
• Ara-U-induced S-phase accumulation and the interaction between high concentrations of ara-U (HiCAU) and ara-C were investigated in L1210 leukemia cells in vitro [5].

High impact information on Ara-U

• THP-1 cells secreted CDA into the incubation media and converted extracellular ara-C completely to 1-beta-D-arabinofuranosyluracil within 30 min [6].
• The concentrations of stearyl-ara-CMP, ara-C (its active metabolite), and 1-beta-D-arabinofuranosyluracil (ara-U, its inactive metabolite) were determined by radioimmunoassay [7].
• Correspondence Re: L.E. Damon et al., Plasma and cerebrospinal fluid pharmacokinetics of 1-beta-D-arabinofuranosylcytosine and 1-beta-D-arabinofuranosyluracil following the repeated intravenous administration of high- and intermediate-dose 1-beta-D-arabinofuranosylcytosine. Cancer Res., 51: 4141-4145, 1991 [8].
• Modulation of the metabolism and pharmacokinetics of 1-beta-D-arabinofuranosylcytosine by 1-beta-D-arabinofuranosyluracil in leukemic mice [9].
• The interaction between high concentrations of 1-beta-D-arabinofuranosyluracil (HiCAU) and 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated in vivo with emphasis on cell kinetics, pharmacokinetics, and drug metabolism [9].

Biological context of Ara-U

• This effect appeared to be primarily due to THU inhibition of ara-C deamination, since a decrease in formation of 1-beta-D-arabinofuranosyluracil in the CSF was observed when ara-C was given in the presence of THU (either i.t. or i.v.). No acute neurotoxicity was noted after administration of either i.t. THU alone or i.t. THU with ara-C [10].
• The ratio of the AUC of Ara-U to the AUC of Ara-C was 0.08, indicating only minor metabolism of Ara-C to Ara-U in CSF, in contrast to that after systemic Ara-C [11].
• Antiherpesviral activity and inhibitory action on cell growth of 5-alkenyl derivatives of 1-beta D-arabinofuranosyluracil [12].

Anatomical context of Ara-U

• However, Ara-CTP/Ara-U ratios from intact myeloblasts were much higher than those recorded in studies using lysed myeloblasts [13].
• Of a series of 5-substituted 1-beta-D-arabinofuranosyluracil (5-X-araU) analogues, (E)-5-(2-bromovinyl)-araU(BrVaraU) and 5-vinyl-araU (VaraU) were the most potent inhibitors of plaque formation by two herpes simplex virus type 1 (HSV-1) strains in human embryonic lung fibroblast (HELF) cell cultures [14].
• We suggest that the high levels of Ara-U in the plasma interfere with Ara-C transport across the blood-brain barrier [15].

Associations of Ara-U with other chemical compounds

• The anti-Ara-C serum obtained from a guinea pig was hardly cross-reactive with 1-beta-D-arabinofuranosyluracil (Ara-U), tetrahydrouridine (THU) and other Ara-C analogues [16].

Gene context of Ara-U

• Accumulation of 1-beta-D-arabinofuranosyluracil 5'-monophosphate was inversely related to the half-life of araCTP retention and directly related to dCMP deaminase activity in cell free extracts [17].
• The concentration of ara-C and 1-beta-D-arabinofuranosyluracil (ara-U), metabolites of PLAC, were measured by radioimmunoassay and gas chromatography-mass spectrometry-mass fragmentography, respectively [18].
• 1-beta-D-Arabinofuranosyluracil (ara-U) level in a cell suspension was suppressed by 6-MP in a concentration-dependent fashion, though intracellular cytidine deaminase (CDD) activity was not affected by 6-MP [19].
• During 6 d of therapy the concentrations of the metabolite Ara-U in the CSF reached rather high levels of between 60 and 70 mumol/l from d 2-6 due to high levels of Ara-U in the plasma [15].

Analytical, diagnostic and therapeutic context of Ara-U

• Conventional and high-dose schedules of ara-C were administered i.v. and intraventricularly through indwelling Ommaya reservoirs. ara-C and its metabolite 1-beta-D-arabinofuranosyluracil (ara-U) were measured by high-pressure liquid chromatography [20].
• Two of four antibodies so obtained showed high specificity for 1-beta-D-arabinofuranosyluracil and allowed the development of a sensitive and reliable radioimmunoassay for this substrate [21].

References