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Natalia Y Tretyakova - One of the best experts on this subject based on the ideXlab platform.

  • Cellular Repair of DNA-DNA Cross-Links Induced by 1,2,3,4-Diepoxybutane.
    International journal of molecular sciences, 2017
    Co-Authors: Lisa N. Chesner, Natalia Y Tretyakova, Amanda Degner, Dewakar Sangaraju, Shira Yomtoubian, Susith Wickramaratne, Bhaskar Malayappan, Colin R Campbell
    Abstract:

    Xenobiotic-induced interstrand DNA–DNA cross-links (ICL) interfere with transcription and replication and can be converted to toxic DNA double strand breaks. In this work, we investigated cellular responses to 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) cross-links induced by 1,2,3,4-Diepoxybutane (DEB). High pressure liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI+-MS/MS) assays were used to quantify the formation and repair of bis-N7G-BD cross-links in wild-type Chinese hamster lung fibroblasts (V79) and the corresponding isogenic clones V-H1 and V-H4, deficient in the XPD and FANCA genes, respectively. Both V-H1 and V-H4 cells exhibited enhanced sensitivity to DEB-induced cell death and elevated bis-N7G-BD cross-links. However, relatively modest increases of bis-N7G-BD adduct levels in V-H4 clones did not correlate with their hypersensitivity to DEB. Further, bis-N7G-BD levels were not elevated in DEB-treated human clones with defects in the XPA or FANCD2 genes. Comet assays and γ-H2AX focus analyses conducted with hamster cells revealed that ICL removal was associated with chromosomal double strand break formation, and that these breaks persisted in V-H4 cells as compared to control cells. Our findings suggest that ICL repair in cells with defects in the Fanconi anemia repair pathway is associated with aberrant re-joining of repair-induced double strand breaks, potentially resulting in lethal chromosome rearrangements.

  • 1,2,3,4-Diepoxybutane-induced DNA-protein cross-linking in human fibrosarcoma (HT1080) cells
    Journal of proteome research, 2013
    Co-Authors: Teshome B. Gherezghiher, Xun Ming, Colin R Campbell, Peter W. Villalta, Natalia Y Tretyakova
    Abstract:

    1,2,3,4-Diepoxybutane (DEB) is the key carcinogenic metabolite of 1,3-butadiene (BD), an important industrial and environmental chemical present in urban air and in cigarette smoke. DEB is a genotoxic bis-electrophile capable of cross-linking cellular biomolecules to form DNA–DNA and DNA–protein cross-links (DPCs). In the present work, mass spectrometry-based proteomics was employed to characterize DEB-mediated DNA–protein cross-linking in human fibrosarcoma (HT1080) cells. Over 150 proteins including histones, high mobility group proteins, transcription factors, splicing factors, and tubulins were found among those covalently cross-linked to chromosomal DNA in the presence of DEB. A large portion of the cross-linked proteins are known factors involved in DNA binding, transcriptional regulation, cell signaling, DNA repair, and DNA damage response. HPLC–ESI+–MS/MS analysis of total proteolytic digests revealed the presence of 1-(S-cysteinyl)-4-(guan-7-yl)-2,3-butanediol conjugates, confirming that DEB form...

  • DNA oligomers containing site-specific and stereospecific exocyclic deoxyadenosine adducts of 1,2,3,4-Diepoxybutane: synthesis, characterization, and effects on DNA structure.
    Chemical research in toxicology, 2010
    Co-Authors: Uthpala Seneviratne, Sergey Antsypovich, Danae Quirk Dorr, Thakshila Dissanayake, Srikanth Kotapati, Natalia Y Tretyakova
    Abstract:

    1,2,3,4-Diepoxybutane (DEB) is a carcinogenic metabolite of 1,3-butadiene (BD), an important industrial and environmental chemical present in urban air and in cigarette smoke. DEB is considered the ultimate carcinogenic species of BD because of its potent genotoxicity and mutagenicity attributed to its ability to form DNA−DNA cross-links and exocyclic nucleoside adducts. Mutagenesis studies suggest that DEB adducts formed at adenine bases may be critically important, as it induces large numbers of A → T transversions. We have recently identified three types of exocyclic DEB-dA lesions: N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (N6,N6-DHB-dA), 1,N6-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (1,N6-γ-HMHP-dA), and 1,N6-(1-hydroxymethyl-2-hydroxypropan-1,3-diyl)-2′-deoxyadenosine (1,N6-α-HMHP-dA) [Seneviratne, U., et al. (2010) Chem. Res. Toxicol. 23, 118−133]. In the work presented here, a postsynthetic methodology for preparing DNA oligomers containing stereospecific and site-s...

  • DNA-protein cross-linking by 1,2,3,4-Diepoxybutane.
    Journal of proteome research, 2010
    Co-Authors: Erin D. Michaelson-richie, Rachel Loeber, Simona G. Codreanu, Xun Ming, Daniel C. Liebler, Colin R Campbell, Natalia Y Tretyakova
    Abstract:

    1,2,3,4-Diepoxybutane (DEB) is a strongly genotoxic diepoxide hypothesized to be the ultimate carcinogenic metabolite of the common industrial chemical and environmental carcinogen 1,3-butadiene. D...

  • Mutagenesis of the supF gene by stereoisomers of 1,2,3,4-Diepoxybutane
    Chemical research in toxicology, 2007
    Co-Authors: Min Young Kim, Natalia Y Tretyakova, Gerald N. Wogan
    Abstract:

    1,2,3,4-Diepoxybutane (DEB) is a key metabolite of the important industrial chemical and environmental contaminant, 1,3-butadiene (BD). Although all three optical isomers of DEB, S,S-, R,R-, and meso-DEB, are produced by metabolic processing of BD, S,S-DEB exhibits the most potent genotoxicity and cytotoxicity, followed by R,R- and then meso-DEB. Our previous studies suggested that the observed differences between the biological effects of DEB optical isomers may be structural in their origin. Although S,S- and R,R-DEB produced mainly 1,3-interstrand 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) cross-links, meso-diepoxide induced equal numbers of intrastrand and interstrand bis-N7G-BD lesions. In the present study, the mutagenicity of the three DEB stereoisomers in the supF gene was investigated. We found that S,S-DEB was the most potent mutagen. Interestingly, mutation specificity and mutant spectra were strongly dependent on DEB stereochemistry. Although A:T to T:A transversions were the major form o...

Margareta Törnqvist - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of molecularly imprinted solid phase extraction for a 1 2 3 4 Diepoxybutane adduct to valine
    Journal of Chromatography B, 2010
    Co-Authors: Kristina Möller, Charlotta Fred, Margareta Törnqvist, Ronnie Davies, Ulrika Nilsson
    Abstract:

    A molecularly imprinted polymer, MIP, was prepared and evaluated as SPE sorbent for a cyclicized adduct formed to N-terminal valine (Pyr-Val) in hemoglobin from 1,2:3,4-Diepoxybutane (DEB). This metabolite plays an important role in the carcinogenesis of 1,3-butadiene. The hydrazide of Pyr-Val, formed after hydrazinolysis of hemoglobin, as well as necessary standards was synthesized. The MIP was prepared from methacrylic acid with a structure analogue to the investigated adduct as template and the method was developed for aqueous conditions. Selective desorption was achieved when the sample was washed with water after loading in 10% acetonitrile. The primary interaction with the binding sites in the imprints was most likely of ionic character. Quantification of the Pyr-Val adduct was performed with LC/ESI-MS/MS, yielding an instrumental LOD of 150 pg injected amount.

  • Evaluation of molecularly imprinted solid-phase extraction for a 1,2:3,4-Diepoxybutane adduct to valine ☆
    Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2010
    Co-Authors: Kristina Möller, Charlotta Fred, Margareta Törnqvist, Ronnie Davies, Ulrika Nilsson
    Abstract:

    A molecularly imprinted polymer, MIP, was prepared and evaluated as SPE sorbent for a cyclicized adduct formed to N-terminal valine (Pyr-Val) in hemoglobin from 1,2:3,4-Diepoxybutane (DEB). This metabolite plays an important role in the carcinogenesis of 1,3-butadiene. The hydrazide of Pyr-Val, formed after hydrazinolysis of hemoglobin, as well as necessary standards was synthesized. The MIP was prepared from methacrylic acid with a structure analogue to the investigated adduct as template and the method was developed for aqueous conditions. Selective desorption was achieved when the sample was washed with water after loading in 10% acetonitrile. The primary interaction with the binding sites in the imprints was most likely of ionic character. Quantification of the Pyr-Val adduct was performed with LC/ESI-MS/MS, yielding an instrumental LOD of 150 pg injected amount.

  • A liquid chromatography tandem mass spectrometric method for in vivo dose monitoring of Diepoxybutane, a metabolite of butadiene.
    Rapid communications in mass spectrometry : RCM, 2000
    Co-Authors: Antti Kautiainen, Charlotta Fred, Per Rydberg, Margareta Törnqvist
    Abstract:

    A liquid chromatography tandem mass spectrometric method for in vivo dose monitoring of Diepoxybutane, a metabolite of butadiene

Sergey Antsypovich - One of the best experts on this subject based on the ideXlab platform.

  • DNA oligomers containing site-specific and stereospecific exocyclic deoxyadenosine adducts of 1,2,3,4-Diepoxybutane: synthesis, characterization, and effects on DNA structure.
    Chemical research in toxicology, 2010
    Co-Authors: Uthpala Seneviratne, Sergey Antsypovich, Danae Quirk Dorr, Thakshila Dissanayake, Srikanth Kotapati, Natalia Y Tretyakova
    Abstract:

    1,2,3,4-Diepoxybutane (DEB) is a carcinogenic metabolite of 1,3-butadiene (BD), an important industrial and environmental chemical present in urban air and in cigarette smoke. DEB is considered the ultimate carcinogenic species of BD because of its potent genotoxicity and mutagenicity attributed to its ability to form DNA−DNA cross-links and exocyclic nucleoside adducts. Mutagenesis studies suggest that DEB adducts formed at adenine bases may be critically important, as it induces large numbers of A → T transversions. We have recently identified three types of exocyclic DEB-dA lesions: N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (N6,N6-DHB-dA), 1,N6-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (1,N6-γ-HMHP-dA), and 1,N6-(1-hydroxymethyl-2-hydroxypropan-1,3-diyl)-2′-deoxyadenosine (1,N6-α-HMHP-dA) [Seneviratne, U., et al. (2010) Chem. Res. Toxicol. 23, 118−133]. In the work presented here, a postsynthetic methodology for preparing DNA oligomers containing stereospecific and site-s...

  • exocyclic deoxyadenosine adducts of 1 2 3 4 Diepoxybutane synthesis structural elucidation and mechanistic studies
    Chemical Research in Toxicology, 2010
    Co-Authors: Uthpala Seneviratne, Sergey Antsypovich, Melissa Goggin, Danae Quirk Dorr, Rebecca Guza, Adam Moser, Carrie Thompson, Darrin M. York
    Abstract:

    1,2,3,4-Diepoxybutane (DEB) is considered the ultimate carcinogenic metabolite of 1,3-butadiene, an important industrial chemical and environmental pollutant present in urban air. Although it preferentially modifies guanine within DNA, DEB induces a large number of A → T transversions, suggesting that it forms strongly mispairing lesions at adenine nucleobases. We now report the discovery of three potentially mispairing exocyclic adenine lesions of DEB: N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (compound 2), 1,N6-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (compound 3), and 1,N6-(1-hydroxymethyl-2-hydroxypropan-1,3-diyl)-2′-deoxyadenosine (compound 4). The structures and stereochemistry of the novel DEB-dA adducts were determined by a combination of UV and NMR spectroscopy, tandem mass spectrometry, and independent synthesis. We found that synthetic N6-(2-hydroxy-3,4-epoxybut-1-yl)-2′-deoxyadenosine (compound 1) representing the product of N6-adenine alkylation by DEB spontane...

  • Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-Diepoxybutane: synthesis and stability at physiological pH.
    Chemical research in toxicology, 2007
    Co-Authors: Sergey Antsypovich, Danaè Quirk-dorr, Crystal Pitts, Natalia Y Tretyakova
    Abstract:

    1,2,3,4-Diepoxybutane (DEB) is an important metabolite of 1,3-butadiene, a high volume industrial chemical classified as a human and animal carcinogen. DEB is a bifunctional alkylating agent that e...

R Barale - One of the best experts on this subject based on the ideXlab platform.

Roberto Barale - One of the best experts on this subject based on the ideXlab platform.

  • Persistence of 4-nitroquinoline-1-oxide induced lesions in human lymphocytes.
    Mutation research, 1996
    Co-Authors: Isabella Ponzanelli, Stefano Landi, Roberto Barale
    Abstract:

    Abstract Liquid holding (LH) recovery was matched with three-way differential staining (TWD) to assess the reduction of damage induced in DNA following treatment with 4-nitroquinoline-1-oxide (4NQO) in resting (G0) lymphocytes. Human peripheral lymphocytes (HPL) from three donors were used to evaluate lesion persistence and individual repair capacity. Our data are in contrast to those for Diepoxybutane (Ponzanelli et al., 1995) and suggest that LH recovery is completely inefficient in removing 4NQO induced lesions, which are only partially repaired after one cell cycle.

  • Effect of red cells and plasma blood in determining individual lymphocytes sensitivity to Diepoxybutane assessed by in vitro induced sister chromatid exchanges.
    Mutation research, 1995
    Co-Authors: Stefano Landi, Isabella Ponzanelli, Roberto Barale
    Abstract:

    Abstract Previous authors investigated individual responsiveness to mutagens by assessing cytogenetic damage following gin vitro treatment. Diepoxybutane (DEB) has been used to assess chromosome instability both in repair-deficient and normal subjects. Since bimodal distribution of sister chromatid exchanges (SCEs) or chromosomal aberration (CAs) frequencies has been observed in normal subjects, we investigated the possible factors determining the ‘high-respondent’ phenotype. The bimodal-shaped distribution suggested the presence of a single factor responsible far this phenotype. Our data showed that red blood cells are involved in determining the sensitivity of lymphocytes to DEB induced SCE. The existence of a polymorphic factor in red cells involved in DEB detoxification is suggested.