Development of resistance to cytarabine (AraC) is a major problem in the treatment of patients with acute myeloid leukemia (AML). Inactivation of deoxycytidine kinase (dCK) plays an important role in AraC resistance in vitro. We have identified inactive, alternatively spliced dCK forms in leukemic blasts from patients with resistant AML. Because these dCK-spliced variants were only detectable i...

The Escherichia coli promoter p(BAD), under the control of the AraC protein, drives the expression of mRNA encoding the AraB, AraA, and AraD gene products of the arabinose operon. The binding site of AraC at p(BAD) overlaps the RNA polymerase -35 recognition region by 4 bases, leaving 2 bases of the region not contacted by AraC. This overlap raises the question of whether AraC substitutes for t...

The antimitotic nucleoside cytosine arabinoside (araC) causes apoptosis in postmitotic neurons for which two mechanisms have been suggested: (1) araC directly inhibits a trophic factor-maintained signaling pathway required for survival, effectively mimicking trophic factor withdrawal; and (2) araC induces apoptosis by a p53-dependent mechanism distinct from trophic factor withdrawal. In rat sym...

The araC gene encodes a positive regulatory protein required for L-arabinose utilization in Escherichia coli. Transcription from the araC promoter has been shown to be under positive control by cAMP receptor protein and under negative control by its protein product (autoregulation). This work describes the identification of the region of the araC promoter that interacts with the cAMP receptor p...

Hypersynthesis of araC protein from Escherichia coli has been accomplished. The araC gene was cloned on plasmid pBR322, and some of the noncoding DNA preceding the araC gene was removed by exonuclease digestion. Finally, a DNA fragment containing the lac promoter and ribosome binding site was placed in front the araC gene. By these means the level of araC protein was increased about 5000-fold a...

We applied two experiments useful in the study of ligand-regulated DNA binding proteins to AraC, the dimeric regulator of the Escherichia coli l-arabinose operon. In the absence of arabinose, AraC prefers to loop DNA by binding to two half-sites that are separated by 210 base pairs, and in the presence of arabinose it prefers to bind to adjacently located half-sites. The basis for this ligand-r...

Although the Comet assay, a procedure for quantitating DNA damage in mammalian cells, is considered sensitive, it has never been ascertained that its sensitivity is higher than the sensitivity of other genotoxicity assays in mammalian cells. To determine whether the power of the Comet assay to detect a low level of genotoxic potential is superior to those of other genotoxicity assays in mammali...

maintenance treatment for patients with acute myeloid leukemia (aml) in remission has recently been controversially discussed and even abandoned by several groups. an analysis of 16 published multicenter trials, however, revealed the highest probabilities of relapse free survival (rfs) in the range of 35-42 % at 4-5 years only in patients assigned to maintenance treatment when adult age and int...

Cytosine arabinoside (AraC) is a pyrimidine antimetabolite that kills proliferating cells by inhibiting DNA synthesis. In this paper we report that AraC kills postmitotic rat sympathetic neurons in a fashion similar to the neuronal death that follows nerve growth factor (NGF) deprivation. Postmitotic rat sympathetic neurons were cultured for 1 week in the presence of NGF and then treated with A...