Disease relevance of BROMOURACIL

• The relative concentrations of EcoRI segments in bromouracil-labeled DNA that replicated during selected intervals of the S phase in Friend virus-transformed murine erythroleukemia (MEL) cells were measured [1].
• Phage lambda- and P22 DNAs containing 5-bromouracil are cleaved more slowly by several enzymes (endonucleases HindIII, Hpa I, BamHI) than are thymine-containing DNAs [2].
• DNA base sequence changes induced by bromouracil mutagenesis of lambda phage [3].
• Ultraviolet irradiation of Escherichia coli cells with a low level of 5-bromouracil incorporated produces DNA double-strand breaks by single photochemical events, one such break per 100 single-strand breaks, the latter assayed in alkali-denatured DNA [4].
• Suppression of melanoma cell tyrosinase activity and tumorigenicity after incorporation of bromouracil for one or two cell divisions [5].

High impact information on BROMOURACIL

• To elucidate the mechanism of Fos-Jun interaction with the TRE we have performed UV cross-linking studies using oligonucleotides where thymines were replaced with bromouracil [6].
• Despite recent experiments showing that BrdUrd-induced mutagenesis can be independent of the level of bromouracil (BrUra) substitution [Kaufman, E.R. & Davidson, R.L. (1978) Proc. Natl. Acad. Sci. USA 75, 4982-4986; Aebersold, P.M. (1976) Mutat. Res. 36, 357-362], BrUra.G base mispairs are a major determinant of mutagenesis [7].
• Bromodeoxyuridine mutagenesis in mammalian cells: mutagenesis is independent of the amount of bromouracil in DNA [8].
• One major difference is that 5-bromouracil-mediated photo-cross-linking experiments indicate that Mcm1 is in close proximity to functional groups in the major groove at the center of the recognition site whereas the SRF protein did not exhibit this characteristic [9].
• Using a sensitive and specific mass spectrometric method, we detected two products of myeloperoxidase, 5-chlorouracil and 5-bromouracil, in neutrophil-rich human inflammatory tissue [10].

Chemical compound and disease context of BROMOURACIL

• Spontaneous, 2-aminopurine- and 5-bromouracil-induced mutations at six rII nonsense codons were studied in phage T4 strains possessing wild-type and mutant gene 43 alleles [11].
• Identification of uracil as a major lesion in E. coli DNA following the incorporation of 5-bromouracil, and some of the accompanying effects [12].
• Escherichia coli mutants defective in DNA uracil N-glycosidase (ung-) or endonuclease VI active against apurinic/apyrimidinic sites in DNA (xthA-) exhibit enhanced sensitivity towards 5-bromodeoxyuridine relative to the wild type strain, pointing to involvement of these enzymes in repair of bromouracil-induced lesions in DNA [13].
• Photochemical cross-linking of the cyclic adenosine 3',5' monophosphate receptor protein to Escherichia coli 5-bromouracil-substituted DNA. Role of the effectors [14].
• Effects of p-fluorophenylalanine on the induction of mutations in bacteriophage T4. I. 5-Bromouracil mutagenesis [15].

Biological context of BROMOURACIL

• To test whether ionized base pairs influence polymerase-catalyzed misinsertion rates, we measured the efficiency of forming 5-bromouracil (B), 5-fluorouracil (F), and thymine base pairs with guanine and adenine as a function of pH using avian myeloblastosis reverse transcriptase [16].
• Chromatids were labelled with bromouracil and stained by the fluorescence plus Giemsa technique [17].
• Uncoupling of the induction of mutations and sister-chromatid exchanges by the replication of 5-bromouracil-substituted DNA [18].
• Genetic evidence for the nature, and excision repair, of DNA lesions resulting from incorporation of 5-bromouracil [13].
• Involvement of DNA lesions and SOS functions in 5-bromouracil-induced mutagenesis [19].

Anatomical context of BROMOURACIL

• Taken together, the synergistic induction of the genes may be explained not only by opening of condensed chromatin by distamycin A but also by increase in the binding of 5-bromouracil-containing S/MAR sequences to the nuclear scaffolds [20].
• The eosinophil peroxidase-hydrogen peroxide-bromide system of human eosinophils generates 5-bromouracil, a mutagenic thymine analogue [21].
• The REP mutagenesis protocol, which involves the replication of 5-bromouracil (BrUra)-substituted DNA in the presence of deoxyribonucleoside triphosphate (dNTP) pool imbalance, has been shown to induce both mutations and sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells [18].
• Using a 12 base pair RNA.DNA hybrid, substituted with bromouracil on either the RNA or DNA strand, we have detected by photoaffinity radiolabeling a limited set of proteins able to bind to RNA.DNA hybrids in both Xenopus oocyte extracts and human macrophage extracts [22].
• None of nine infected cell lines treated with 5-bromouracil were consistently cured of mycoplasmas [23].

Associations of BROMOURACIL with other chemical compounds

• In contrast, previous studies have demonstrated that 5-bromouracil could be generated by either eosinophil peroxidase or myeloperoxidase, which preferentially brominates uracil at plasma concentrations of halide and under moderately acidic conditions [10].
• The insertion of bromouracil occurring in direct competition with cytosine deoxyribonucleotides opposite template guanine sites is 1.1 +/- 0.14% (mean +/- S.E.), and the misincorporation ratio, inc(B)/inc(C), is reduced 6-fold by the action of the proofreading exonuclease to 0.16 +/- 0.02% (mean +/- S.E.). A previous study by Trautner et al [24].
• Further confirmation of this conclusion was obtained by substitution of 5-bromocytosine and 5-bromouracil at this base pair [25].
• The method is based on the photolysis of bromouracil-containing DNA by 313 nm light and alkaline sucrose gradients [26].
• In UAA sites, all three adenine:thymidine paris respond to 2AP mutagenesis in a similar pattern, In each position in the triplet, response to 2 AP is correlated with that to 5BU [27].

Gene context of BROMOURACIL

• Mutants with genotype thyA- dra- discriminate against bromouracil to much greater extent than do mutants with genotype thyA- drm-. 2 [28].
• When removal of UVR-induced photoproducts was initiated by endogenous excision repair mechanisms, an average of 38 nucleotides were replaced per dimer removed, as determined by bromouracil photolysis; denV-initiated excision repair, on the other hand, resulted in removal of an average of 6 nucleotides per dimer repaired [29].
• Except for mutants of mutT type, these mutators also showed high mutability by bromouracil [30].
• Discrimination between bromouracil and thymine for uptake into DNA in drm- and dra- mutants of Escherichia coli K12 [28].
• Mutagenesis by 5-bromouracil of lambda phage to clear plaque formers does not depend on the recA function of the host E. coli cell or on the red function of the phage [31].

Analytical, diagnostic and therapeutic context of BROMOURACIL

• The product was identified as 5-bromouracil by mass spectrometry, HPLC, and UV--visible spectroscopy [21].
• Blood and plasma concentrations of FU and dFUR were analyzed by high-pressure liquid chromatography using 5-bromouracil as the internal standard [32].
• Under varying growth conditions the percentage of thymine replacement by bromouracil in DNA, as determined by gas chromatography/mass spectrometry analysis, declined as cultures approached maximum density [33].
• Electron transfer to 5-bromouracil (5-BrU) from nucleobase (N) electron adducts (and their protonated forms) has been studied by product analysis and pulse radiolysis [34].
• Experiments with the centrifugation of non-sheared and sonicated 5-bromouracil and [3H]dAMP-labeled mitochondrial DNA (mtDNA) in alkaline CsCl density gradients provided evidence of a covalent linkage between newly-synthesized stretches and the parental DNA strands [35].

References