Disease relevance of O-methylhydroxylamine

• Methoxyamine not only was able to increase IdUrd cytotoxicity but also increased the incorporation of IdUrd into DNA of HCT116 human colon cancer cells leading to greater radiosensitization [1].
• Methoxylamine mutagenesis of the beta-galactosidase gene from Lactobacillus delbrückii subsp. bulgaricus was used to generate cold-sensitive variants [2].
• A restriction fragment is inserted in each orientation into an M13 vector, single-stranded virion DNA from each recombinant phage is treated with methoxylamine, and, after reannealing of the mutagenized strands, a double-stranded restriction fragment is obtained [3].
• By using a model oligonucleotide containing a single AP site modified with methoxyamine (MX), we show that endonuclease III and IV of E. coli are able to cleave the alkoxyamine-adducted site whereas a partially purified HeLa AP endonuclease and crude cell-free extracts from HeLa cells are inhibited by this modification [4].
• We conclude that methoxyamine enhances manumycin-induced apoptosis in myeloid leukemia cells [5].

High impact information on O-methylhydroxylamine

• Duplicate samples heated in the presence of methoxyamine to protect the apurinic sites from alkaline hydrolysis provided controls to assess total DNA [6].
• Consistent with our recent publication, coadministration of IdUrd and a chemical inhibitor of BER, methoxyamine (MX), also increases the extent of MSH2 nuclear colocalization with IdUrd [7].
• We also assessed the role of methoxyamine, a small molecule inhibitor of BER, in the response of human colon cancer cells (HCT116) to IdUrd cytotoxicity and radiosensitization [1].
• Because methoxyamine-mediated sensitization of beta-pol wild-type and beta-pol-complemented cells to GCV did not reach the level of null cells, we suggest that both beta-pol-dependent short- and long-patch base excision repair are involved in protection of cells to GCV [8].
• Mutagenic processing of ethylation damage in mammalian cells: the use of methoxyamine to study apurinic/apyrimidinic site-induced mutagenesis [9].

Chemical compound and disease context of O-methylhydroxylamine

• The replication of the phage MS2 in the presence of either hydroxylamine (HA) or O-methylhydroxylamine (OMHA) (mutagenesis in vivo) results in an increase in the reversion frequency of two amber mutations in the maturation protein [10].
• O-Methylhydroxylamine (methoxyamine) was used for selective modification of cytosine residues in Escherichia coli 16-S rRNA [11].
• To refine the secondary structure model of the 5' end of the bacteriophage MS2 genome, 32P-labeled MS2 RNA was partially digested with T1 RNase or with Cm-RNase and the 5'-end fragment was isolated, renatured and submitted to treatment with methoxyamine or kethoxal [12].
• Characterization of inactivation of myxoviruses and paramyxoviruses by hydroxylamine, N-methylhydroxylamine and O-methylhydroxylamine [13].

Biological context of O-methylhydroxylamine

• Plasmid molecules were heat-treated at pH 5 and incubated with MX when required [14].
• Methoxyamine modification of abasic sites protects CHO cells from the cytotoxic and mutagenic effects of oxygen alkylation [15].
• Since repair of DNA damage is important to cell survival, we hypothesized that methoxyamine, an inhibitor of base-excision repair, would enhance the antineoplastic effect of manumycin [5].
• The results are considered in relation to hydroxylamine and methoxyamine mutagenesis, to types of base-pairing at the monomer and polymer levels, and to interpretations of 15N NMR spectra of heterocyclic rings in general [16].
• Thus, senescence, a novel ionizing radiation-induced tumor suppression pathway, may be effectively targeted by IUdR/methoxyamine pretreatment, resulting in an improved therapeutic gain for ionizing radiation [17].

Anatomical context of O-methylhydroxylamine

• Pretreatment of cells with methoxyamine as a DNA repair modifier blocking the base excision repair pathway revealed a quite similar extent of base excision repair-independent DNA incision in almost all normal lymphocyte samples [18].
• The biological effects of the interaction of methoxyamine (MX) with apurinic/apyrimidinic (AP) sites produced in CHO cells by treatment with alkylating agents were examined [15].
• Incubation of L-739,010 with methoxylamine and hepatic microsomes from dog, rhesus monkey, and human produced similar metabolic adducts as those formed by rat liver microsomes [19].
• The binding of O-methylhydroxylamine-modified f2 [14C]RNA to E. coli 70-S or 20-S ribosomes does not depend on the presence of initiation factors [20].
• 8-Oxoguanine-DNA-glycosylase 1-/- (OGG1-/-) mouse embryonal fibroblasts and human fibroblasts in which BER was inhibited by incubation with methoxyamine were hypersensitive to UVA1, in particular to low doses [21].

Associations of O-methylhydroxylamine with other chemical compounds

• Expression of beta-pol in the null cells restores the ability of MX to modulate sensitivity to MMS [22].
• The relevance of these results to the molecular basis of hydroxylamine and methoxyamine mutagenesis and to the phenomenon of proton exchange in other systems is briefly discussed [23].
• These adducts were characterized by examination of their mass spectra, by analysis of the products of their reaction with sodium cyanide, sodium borohydride, and methoxylamine and by the mass spectra derived from collision-induced dissociation in tandem mass spectrometry [24].
• For this aim plasmid DNA was cleaved at the BamHI site, and cytosine residues of the sticky ends were modified by O-methylhydroxylamine [25].
• The methoxyamine-treated aliquot provided gene fragments which were refractory to alkaline hydrolysis (full-length fragments), while the fragments in the untreated aliquot were cleaved at apurinic sites by hydroxide [26].

Gene context of O-methylhydroxylamine

• The severe MMS sensitivity seen in AP endonuclease deficient strains can also be rescued by treatment of cells with the AP lyase inhibitor methoxyamine, which suggests that the product of AP lyase action on an AP site is indeed an extremely toxic lesion [27].
• The rpsH gene, which encodes protein S8, was first inserted into an expression vector under the control of the lac promoter and subsequently mutagenized with methoxylamine or nitrous acid [28].
• MGMT inhibitors, PARP inhibitors and methoxyamine are currently in early stages of clinical development [29].
• We also show that 4-Amino-1,8-naphthalimide (4-AN, inhibitor of PARP) but not methoxyamine (inhibitor of base excision repair (BER)), affects IR induced G2 arrest and cell sensitivity in PARP-1+/+ cells, resulting in the phenotypes similar to those of PARP-1-/- cells [30].
• The mechanism of interaction of methoxyamine with sheep liver serine hydroxymethyltransferase (EC 2.1.2.1) (SHMT) was established by measuring changes in enzyme activity, visible absorption spectra, circular dichroism and fluorescence, and by evaluating the rate constant by stopped-flow spectrophotometry [31].

Analytical, diagnostic and therapeutic context of O-methylhydroxylamine

• After alkaline hydrolysis, agarose gel electrophoresis, Southern transfer, and probing for the fragment of interest, the ratios of band intensities of the test DNA sample to its methoxyamine-treated control counterpart were calculated to yield the percentage of fragments containing no alkaline-labile sites [6].
• This O-methylhydroxylamine is separated by reversed-phase high-performance liquid chromatography and quantified fluorometrically [32].
• N4-Methoxydeoxycytidine 5'-triphosphate (mo4dCTP) was synthesized by reaction of dCTP with methoxyamine and then purified by high-performance liquid chromatography (HPLC) and used to analyze the specificity of mo4dCMP incorporation during polymerization on natural templates, catalyzed by DNA polymerase I of Escherichia coli [33].
• Catecholamine (CA) and methoxyamine levels were essentially unaltered at any time of bed rest [34].
• These products were purified by t.l.c., derivatized by treatment with methoxyamine, diazomethane, and N,O-bis-(trimethylsily1)-trifluoroacetamide, and these derivatives used for gas chromatography and gas chromatography-mass spectrometry [35].

References