当前位置： SCI文献检索 > CHEMICAL RESEARCH IN TOXICOLOGY期刊下所有文献 > Oxidative bioactivation of abacavir in subcellular fractions of human antigen presenting cells.

Oxidative bioactivation of abacavir in subcellular fractions of human antigen presenting cells.

Abstract：

:Human exposure to abacavir, a primary alcohol antiretroviral, is associated with the development of immunological drug reactions in individuals carrying the HLA risk allele B*57:01. Interaction of abacavir with antigen presenting cells results in cell activation through an Hsp70-mediated Toll-like receptor pathway and the provision of T-cell antigenic determinants. Abacavir's electrophilic aldehyde metabolites are potential precursors of neoantigens. Herein, we have used mass spectrometry to study the oxidative metabolism of abacavir in EBV-transformed human B-cells. RNA and protein were isolated from the cells and subjected to transcriptomic and mass spectrometric analyses to identify the redox enzymes expressed. Low levels of isomeric abacavir carboxylic acids were detected in subcellular fractions of EBV-transformed human B-cells incubated with abacavir. Metabolite formation was time-dependent but was not reduced by an inhibitor of Class I alcohol dehydrogenases. Relatively high levels of mRNA were detected for several redox enzymes, including alcohol dehydrogenase 5 (Class III), aldehyde dehydrogenases (ALDH3A2, ALDH6A1, and ALDH9A1), CYP1B1, CYP2R1, CYP7B1, and hydroxysteroid dehydrogenase 10. Over 2600 proteins were identified by mass spectrometry. More than 1000 of these proteins exhibited catalytic activity, and 80 were oxido-reductases. This is the first proteomic inventory of enzymes in antigen presenting cells. However, neither of the hepatic alcohol dehydrogenases of Class I which metabolize abacavir in vitro was expressed at the protein level. Nevertheless the metabolic production of abacavir carboxylic acids by B-cell fractions implies abacavir-treated immune cells might be exposed to the drug's protein-reactive aldehyde metabolites in vivo.

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Bell CC,Santoyo Castelazo A,Yang EL,Maggs JL,Jenkins RE,Tugwood J,O'Neill PM,Naisbitt DJ,Park BK

doi

10.1021/tx400041v

subject

Has Abstract

pub_date

2013-07-15 00:00:00

pages

1064-72

issue

7

eissn

0893-228X

issn

1520-5010

journal_volume

26

pub_type

杂志文章

相关文献

CHEMICAL RESEARCH IN TOXICOLOGY文献大全
  • Thiol oxidation by 1,2,3-oxadiazolinium ions, presumed carcinogens.

    abstract：:3-Alkyl-1,2,3-oxadiazolinium ions 1 have been proposed as reactive intermediates in the activation of (2-hydroxyethyl)nitrosamines. The reaction of 3-methyl-1,2,3-oxadiazolinium tosylate (1a), 2-ethyl-1-methoxy-2-phenyldiazenium tetrafluoroborate (3), and 3-phenyl-1,2,3-oxadiazolinium triflate (1b) with thiols was inv...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00048a001

    authors： Loeppky RN,Srinivasan A

    更新日期：1995-09-01 00:00:00

  • Metabolic studies on the nigrostriatal toxin MPTP and its MAO B generated dihydropyridinium metabolite MPDP+.

    abstract：:The metabolic fates of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its two-electron oxidation product, the 1-methyl-4-phenyl-2,3-dihydropyridinium species (MPDP+), have been examined in mouse brain and liver tissue fractions. Incubations of MPTP (50 microM and 1 mM) with mouse brain...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00003a010

    authors： Wu E,Shinka T,Caldera-Munoz P,Yoshizumi H,Trevor A,Castagnoli N Jr

    更新日期：1988-05-01 00:00:00

  • Identification of Quinone Methide Intermediate Resulting from Metabolic Activation of Icaritin in Vitro and in Vivo.

    abstract：:Many herbal medicines such as epimedium have been reported to cause adverse effects, and icaritin is the common aglycone of many glucosides in epimedium. Our present work aimed at the clarification of the metabolic activation of icaritin possibly responsible for the adverse effects of epimedium. A quinone methide meta...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.8b00418

    authors： Chen Y,Guo X,Ma Y,Hu X,Peng Y,Zheng J

    更新日期：2019-06-17 00:00:00

  • Identification of novel metabolites of butadiene monoepoxide in rats and mice.

    abstract：:Differences in the metabolism of 1,3-butadiene (Bd) in rats and mice may account for the observed species difference in carcinogenicity. Previous studies of the metabolic fate of Bd have identified epoxide formation as a key metabolic transformation which gives 1, 2-epoxy-3-butene (BMO), although some evidence of alde...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx970175v

    authors： Richardson KA,Peters MM,Megens RH,van Elburg PA,Golding BT,Boogaard PJ,Watson WP,van Sittert NJ

    更新日期：1998-12-01 00:00:00

  • Cyclic imines: chemistry and mechanism of action: a review.

    abstract：:In recent years, there has been an increase in the production of shellfish and in global demand for seafood as nutritious and healthy food. Unfortunately, a significant number of incidences of shellfish poisoning occur worldwide, and microalgae that produce phycotoxins are responsible for most of these. Phycotoxins in...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章,评审

    doi：10.1021/tx200182m

    authors： Otero A,Chapela MJ,Atanassova M,Vieites JM,Cabado AG

    更新日期：2011-11-21 00:00:00

  • Cyclooxygenase-2 expression is up-regulated by 2-aminobiphenyl in a ROS and MAPK-dependent signaling pathway in a bladder cancer cell line.

    abstract：:Overexposure to biphenyl amine compounds, which are found in smoke and azo-dyes, is linked to the occurrence of bladder cancer. However, the molecular mechanisms of biphenyl amine compound-induced bladder cancer are still unclear. Many studies have demonstrated that overexpression of cyclooxygenase-2 (COX-2) in neopla...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx2004689

    authors： Chen CC,Cheng YY,Chen SC,Tuan YF,Chen YJ,Chen CY,Chen LC

    更新日期：2012-03-19 00:00:00

  • Nitroxidative, nitrosative, and nitrative stress: kinetic predictions of reactive nitrogen species chemistry under biological conditions.

    abstract：:A freely available Windows-based program, RNSim1A, is utilized to predict metal-independent reactive nitrogen species (RNS) chemistry (oxidation, nitrosation, and nitration) under simulated biological conditions and make the following specific predictions. (1) The peak in oxidative reactions that occurs in vitro with ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx060061w

    authors： Lancaster JR Jr

    更新日期：2006-09-01 00:00:00

  • (-)-Epigallocatechin gallate, a major constituent of green tea, poisons human type II topoisomerases.

    abstract：:(-)-Epigallocatechin gallate (EGCG) is the most abundant and biologically active polyphenol in green tea, and many of the therapeutic benefits of the beverage have been attributed to this compound. High concentrations of EGCG are cytotoxic and trigger genotoxic events in mammalian cells. Although this catechin affects...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx700434v

    authors： Bandele OJ,Osheroff N

    更新日期：2008-04-01 00:00:00

  • Renal elimination of perfluorocarboxylates (PFCAs).

    abstract：:Sex-, species-, and chain length-dependent renal elimination is the hallmark of mammalian elimination of perfluorocarboxylates (PFCAs) and has been extensively studied for almost 30 years. In this review, toxicokinetic data of PFCAs (chain lengths ranging from 4 to 10) in different species are compared with an emphasi...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章,评审

    doi：10.1021/tx200363w

    authors： Han X,Nabb DL,Russell MH,Kennedy GL,Rickard RW

    更新日期：2012-01-13 00:00:00

  • Reactivity with Tris(hydroxymethyl)aminomethane confounds immunodetection of acrolein-adducted proteins.

    abstract：:The toxic alpha,beta-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biol...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx0341106

    authors： Burcham PC,Fontaine FR,Petersen DR,Pyke SM

    更新日期：2003-10-01 00:00:00

  • Polymerase Bypass of N(6)-Deoxyadenosine Adducts Derived from Epoxide Metabolites of 1,3-Butadiene.

    abstract：:N(6)-(2-Hydroxy-3-buten-1-yl)-2'-deoxyadenosine (N(6)-HB-dA I) and N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (N(6),N(6)-DHB-dA) are exocyclic DNA adducts formed upon alkylation of the N(6) position of adenine in DNA by epoxide metabolites of 1,3-butadiene (BD), a common industrial and environmental che...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.5b00166

    authors： Kotapati S,Wickramaratne S,Esades A,Boldry EJ,Quirk Dorr D,Pence MG,Guengerich FP,Tretyakova NY

    更新日期：2015-07-20 00:00:00

  • Chromium(VI) causes interstrand DNA cross-linking in vitro but shows no hypersensitivity in cross-link repair-deficient human cells.

    abstract：:Hexavalent chromium is a human carcinogen activated primarily by direct reduction with cellular ascorbate and to a lesser extent, by glutathione. Cr(III), the final product of Cr(VI) reduction, forms six bonds allowing intermolecular cross-linking. In this work, we investigated the ability of Cr(VI) to cause interstra...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx400293s

    authors： Morse JL,Luczak MW,Zhitkovich A

    更新日期：2013-10-21 00:00:00

  • Metabolic activation and major protein target of a 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonist.

    abstract：:1-{4-[(4-Phenyl-5-trifluoromethyl-2-thienyl)methoxy]benzyl}azetidine-3-carboxylic acid (MRL-A) is a potent sphingosine-1-phosphate-1 receptor agonist, with potential application as an immunosuppressant in organ transplantation or for the treatment of autoimmune diseases. When administered orally to rats, radiolabeled ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx300017s

    authors： Aloysius H,Tong VW,Yabut J,Bradley SA,Shang J,Zou Y,Tschirret-Guth RA

    更新日期：2012-07-16 00:00:00

  • Role of hydrophobic effects in the reaction of a polynuclear aromatic diol epoxide with oligodeoxynucleotides in aqueous solutions.

    abstract：:The need for large-scale direct synthesis of stereochemically defined and site-specific benzo[alpha]pyrenediol epoxide-oligodeoxyribonucleotide adducts for detailed NMR and other biochemical and physicochemical studies has necessitated a better understanding of variables that lead to an enhancement of the reaction yie...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx980006q

    authors： Pirogov N,Shafirovich V,Kolbanovskiy A,Solntsev K,Courtney SA,Amin S,Geacintov NE

    更新日期：1998-04-01 00:00:00

  • Oxidative DNA damage following microsome/Cu(II)-mediated activation of the estrogens, 17β-estradiol, equilenin, and equilin: role of reactive oxygen species.

    abstract：:Experimental and epidemiological data associate the exposure of estrogens to cancer development in several tissues, particularly, the breast, endometrium, liver, and kidney. One plausible mechanism of estrogen-mediated carcinogenicity is DNA damage by redox cycling of estrogen catechols. Reports have shown that metabo...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx200356v

    authors： Spencer WA,Vadhanam MV,Jeyabalan J,Gupta RC

    更新日期：2012-02-20 00:00:00

  • Bezafibrate induces a mitochondrial derangement in human cell lines: a PPAR-independent mechanism for a peroxisome proliferator.

    abstract：:Bezafibrate is a hypolipidemic drug that belongs to the group of peroxisome proliferators because it binds to peroxisome proliferator-activated receptors type alpha (PPARs). Peroxisome proliferators produce a myriad of extraperoxisomal effects, which are not necessarily dependent on their interaction with PPARs. An in...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx0341052

    authors： Scatena R,Bottoni P,Vincenzoni F,Messana I,Martorana GE,Nocca G,De Sole P,Maggiano N,Castagnola M,Giardina B

    更新日期：2003-11-01 00:00:00

  • The reactivity of the 5-hydroxy-5,6-dihydrothymidin-6-yl radical in oligodeoxyribonucleotides.

    abstract：:Hydroxyl radical can be induced from Fenton reaction or gamma radiolysis of water. It can add preferentially to the C5 position of thymidine to give the 5-hydroxy-5,6-dihydrothymidin-6-yl radical. In this report, we examined the independent generation and reactivity of this radical in oligodeoxyribonucleotides (ODNs)....

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx050195u

    authors： Zhang Q,Wang Y

    更新日期：2005-12-01 00:00:00

  • A study of inactivation reactions of N-acetylcysteine with mucochloric acid, a mutagenic product of the chlorination of humic substances in water.

    abstract：:The Salmonella typhimurium (TA100) mutagenic compound, mucochloric acid [3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA)], was inactivated by in vitro N-acetylcysteine (NAC). The reaction of MCA with NAC at pH7 was second order and gave products 4, 5, and 6a that resulted from the displacement of chlorine from C-3 or C-4 ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00029a005

    authors： LaLonde RT,Xie S

    更新日期：1992-09-01 00:00:00

  • AHR- and DNA-damage-mediated gene expression responses induced by benzo(a)pyrene in human cell lines.

    abstract：:Carcinogens induce complex transcriptional responses in cells that may hold key mechanistic information. Benzo(a)pyrene (BaP) modulation of transcription may occur through the activation of the aryl hydrocarbon receptor (AHR) or through responses to DNA damage. To characterize further the expression profiles induced b...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx700252n

    authors： Hockley SL,Arlt VM,Brewer D,Te Poele R,Workman P,Giddings I,Phillips DH

    更新日期：2007-12-01 00:00:00

  • Thioproline Serves as an Efficient Antioxidant Protecting Human Cells from Oxidative Stress and Improves Cell Viability.

    abstract：:Oxidative stress is associated with the pathophysiology of many degenerative human diseases, including Alzheimer's disease, atherosclerosis, Parkinson's disease, and cancers. We discovered in our previous study that thioproline (SPro), a proline analogue, is generated in oxidant-exposed cells. With the prior observati...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.0c00055

    authors： Ham YH,Jason Chan KK,Chan W

    更新日期：2020-07-20 00:00:00

  • Chlorine dioxide oxidations of tyrosine, N-acetyltyrosine, and dopa.

    abstract：:The reactions of aqueous ClO2 with tyrosine, N-acetyltyrosine, and dopa (3,4-dihydroxyphenylalanine) are investigated from pH 4 to 7. The reaction rates increase greatly with pH to give a series of oxidized products. Tyrosine and N-acetyltyrosine have similar reactivities with second-order rate constants (25.0 degrees...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049697i

    authors： Napolitano MJ,Green BJ,Nicoson JS,Margerum DW

    更新日期：2005-03-01 00:00:00

  • Improved efficacy of acylfulvene in colon cancer cells when combined with a nuclear excision repair inhibitor.

    abstract：:The efficacy of DNA-damaging anticancer drugs is highly influenced by cellular DNA repair capacity, and by inhibiting the relevant DNA repair pathway, efficacy of alkylating agents may be increased. Therefore, combining DNA repair inhibitors with anticancer agents that selectively target tumor tissue should improve ca...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx400255f

    authors： van Midwoud PM,Sturla SJ

    更新日期：2013-11-18 00:00:00

  • Molecular characteristics of catechol estrogen quinones in reactions with deoxyribonucleosides.

    abstract：:Estrogens can have two roles in the induction of cancer: stimulating proliferation of cells by receptor-mediated processes, and generating electrophilic species that can covalently bind to DNA. The latter role is thought to proceed through catechol estrogen metabolites, which can be oxidized to o-quinones that bind to...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx960002q

    authors： Stack DE,Byun J,Gross ML,Rogan EG,Cavalieri EL

    更新日期：1996-07-01 00:00:00

  • Quantitative component analysis of mixtures for risk assessment: application to eye irritation.

    abstract：:A methodology called quantitative component analysis of mixtures (QCAM) was used to analyze an existing set of product formulation data to determine if the irritating ingredients in the mixtures could be identified. Eye irritation scores, based on a rat model, for 18 mixtures having a composite total of 37 components,...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx990098z

    authors： Patel HC,Duca JS,Hopfinger AJ,Glendening CD,Thompson ED

    更新日期：1999-11-01 00:00:00

  • Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease.

    abstract：:The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum and in vitro in PC12 cells and human cultured fibroblasts and glial cells. The in vi...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx5002223

    authors： Casida JE,Ford B,Jinsmaa Y,Sullivan P,Cooney A,Goldstein DS

    更新日期：2014-08-18 00:00:00

  • Peroxynitrite-dependent tryptophan nitration.

    abstract：:Peroxynitrite (ONOO-), the reaction product of superoxide (O2.-) and nitric oxide (.NO), nitrates tyrosine and other phenolics. We report herein that tryptophan is also nitrated by peroxynitrite in the absence of transition metals to one predominant isomer of nitrotryptophan, as determined from spectral characteristic...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx950133b

    authors： Alvarez B,Rubbo H,Kirk M,Barnes S,Freeman BA,Radi R

    更新日期：1996-03-01 00:00:00

  • Regioisomeric synthesis and characteristics of the alpha-hydroxy-1,N(2)-propanodeoxyguanosine.

    abstract：:Acrolein, a known mutagen, undergoes reaction in vitro under physiological conditions with both 2'-deoxyguanosine and native DNA to give rise to exocyclic adducts of the 5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one class having a hydroxyl group at either the 6 or the 8 position (these positions are respectively ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx015568f

    authors： Huang Y,Johnson F

    更新日期：2002-02-01 00:00:00

  • The stepwise process of chromium-induced DNA breakage: characterization by electrochemistry, atomic force microscopy, and DNA electrophoresis.

    abstract：:DNA conformational change and breakage induced by Cr(VI)-GSH interaction were characterized by the integrated tools of electrochemistry, atomic force microscopy (AFM), and DNA electrophoresis. While electrochemistry confirmed the formation of the active species generated from Cr(VI)-GSH reduction, which causes the DNA...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx050134w

    authors： Yang PH,Gao HY,Cai J,Chiu JF,Sun H,He QY

    更新日期：2005-10-01 00:00:00

  • Occupational Respiratory Exposure to Platinum Group Metals: A Review and Recommendations.

    abstract：:Platinum group metals (PGMs) is a group of metals that include platinum, palladium, rhodium, ruthenium, iridium, and osmium. Occupational respiratory exposure to platinum has been reported since 1945, but studies investigating occupational exposure to palladium, rhodium, ruthenium, iridium, and osmium are scarce. This...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章,评审

    doi：10.1021/acs.chemrestox.7b00184

    authors： Linde SJL,Franken A,du Plessis JL

    更新日期：2017-10-16 00:00:00

  • Comparison of Free Radical Levels in the Aerosol from Conventional Cigarettes, Electronic Cigarettes, and Heat-Not-Burn Tobacco Products.

    abstract：:Aerosols from electronic cigarettes and heat-not-burn tobacco products have been found to contain lower levels of almost all compounds from the list of Harmful and Potentially Harmful Constituents known to be present in tobacco products and tobacco smoke than smoke from conventional cigarettes. Free radicals, which al...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00085

    authors： Shein M,Jeschke G

    更新日期：2019-06-17 00:00:00