Monitoring Cr intermediates and reactive oxygen species with fluorescent probes during chromate reduction.


:Cr(VI) genotoxicity is caused by products of its reductive metabolism inside the cells. Reactive oxygen species (ROS) and Cr(V,IV) intermediates are potential sources of oxidative damage by Cr(VI). Here, we investigated seven fluorescent probes for the detection of ROS and non-ROS oxidants in Cr(VI) reactions with its main reducers. We found that Cr(V)-skipping metabolism of Cr(VI) by ascorbate in vitro gave no responses with all tested dyes, indicating nonreactivity of Cr(IV) and absence of ROS. Cr(VI) reduction with glutathione (GSH) or Cys strongly enhanced the fluorescence of dichlorofluorescein (DCF) and dihydrorhodamine 123 (DHR123) but produced minimal fluorescence with dihydroethidium and no increases with aminophenylfluorescein and CellRox Green, Orange, and Red. Several tests showed that Cr(VI)-thiol reactions lacked ROS and that Cr(V) caused oxidation of DCF and DHR123. DCF reacted only with free Cr(V), whereas DHR123 detected both the free Cr(V) and Cr(V)-GSH complex. We estimated that Cr(VI)-GSH reactions generated approximately 75% Cr(V)-GSH and 25% free Cr(V), whereas Cys reactions appeared to produce only free Cr(V). DHR123 measurements in H460 cells showed that reduction of Cr(VI) was complete within 20 min postexposure, but it lasted at least 1 h without GSH. Cells with restored ascorbate levels exhibited no DCF or DHR123 oxidation by Cr(VI). Overall, our results demonstrated that Cr(VI) metabolism with its biological reducers lacked ROS and that DHR123 and DCF responses were indicators of total and free Cr(V), respectively. CellRox dyes, dihydroethidium and aminophenylfluorescein, are insensitive to Cr(V,IV) and can be used for monitoring ROS during coexposure to Cr(VI) and oxidants.


Chem Res Toxicol


DeLoughery Z,Luczak MW,Zhitkovich A




Has Abstract


2014-05-19 00:00:00












  • Is diacetyl a respiratory sensitizer? A reconsideration using QSAR, QMM, and competition experiments.

    abstract::Concerns have been raised that diacetyl (DA) might be a respiratory sensitizer based on its LUMO energy similar to that of the respiratory allergen toluene-2,4-diisocyanate (TDI) and results of a local lymph node assay (LLNA) that reported an EC3 of 1.9%. To better understand the concerns, we performed a systematic li...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章,评审


    authors: Dworak JJ,Roberts DW,Calter MA,Fields CA,Borak J

    更新日期:2013-05-20 00:00:00

  • Benzo[a]pyrene diol epoxide forms covalent adducts with deoxycytidylic acid by alkylation at both exocyclic amino N(4) and ring imino N-3 positions.

    abstract::The carcinogen 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) alkylates DNA at dGuo, dAdo, and dCyd. dCyd adducts, formed in small amounts, elute near the more abundant dGuo adducts. We isolated the dCyd adducts formed with dCMP. Each BPDE enantiomer forms three major adducts with dCMP, two...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Wolfe AR,Smith TJ,Meehan T

    更新日期:2004-04-01 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


    authors: Morse JL,Luczak MW,Zhitkovich A

    更新日期:2013-10-21 00:00:00

  • Lipid peroxidation-dependent chemiluminescence from the cyclization of alkylperoxyl radicals to dioxetane radical intermediates.

    abstract::This work reveals a novel mechanism for triplet carbonyl formation (and hence chemiluminescence) during lipid peroxidation, whose chemiluminescence has been attributed to both triplet carbonyls and singlet oxygen. As a model for polyunsaturated fatty acid hydroperoxides, we have synthesized 3-hydroperoxy-2,3-dimethyl-...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Tímmins GS,dos Santos RE,Whitwood AC,Catalani LH,Di Mascio P,Gilbert BC,Bechara EJ

    更新日期:1997-10-01 00:00:00

  • Intersection of the Roles of Cytochrome P450 Enzymes with Xenobiotic and Endogenous Substrates: Relevance to Toxicity and Drug Interactions.

    abstract::Today much is known about cytochrome P450 (P450) enzymes and their catalytic specificity, but the range of reactions catalyzed by each still continues to surprise. Historically, P450s had been considered to be involved in either the metabolism of xenobiotics or endogenous chemicals, in the former case playing a genera...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Guengerich FP

    更新日期:2017-01-17 00:00:00

  • Reduced Transcriptomic Approach for Screening and Prediction of Chemical Toxicity.

    abstract::The reduced transcriptomic approach allows full dose range testing of hundreds of chemicals or mixtures using human cells or zebrafish embryos. Points of departure of genes and pathways can be used for potency ranking and to classify chemicals by disrupted biological pathways. ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Dai J

    更新日期:2018-07-16 00:00:00

  • Sucralose-Enhanced Degradation of Electronic Cigarette Liquids during Vaping.

    abstract::Electronic cigarette liquids (e-liquids) with sweetener additives such as sucralose, a synthetic chlorinated disaccharide, are popular among some e-cigarette consumers; sucralose can be added either by the manufacturer or by the consumer. The prevalence of sucralose in commercial e-liquids is not known, nor is the typ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Duell AK,McWhirter KJ,Korzun T,Strongin RM,Peyton DH

    更新日期:2019-06-17 00:00:00

  • Harmful and beneficial effects of organic monosulfides, disulfides, and polysulfides in animals and humans.

    abstract::Many organic sulfides (mono-, di-, and polysulfides) are present in our environment. Simple derivatives are produced by some plants and animals, while complex sulfides are secondary metabolites of several genera of bacteria and fungi. Sulfides play an important role in the smell and taste of food, and many such compou...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章,评审


    authors: Munday R

    更新日期:2012-01-13 00:00:00

  • Quartz Disrupts Iron Homeostasis in Alveolar Macrophages To Impact a Pro-Inflammatory Effect.

    abstract::The biological response of bronchial epithelial cells to particles is associated with a sequestration of cell metal by the particle surface and a subsequent disruption in host iron homeostasis. The macrophage is the cell type resident in the respiratory tract that is most likely to make initial contact with inhaled pa...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Ghio AJ,Soukup JM,Stonehuerner J,Tong H,Richards J,Gilmour MI,Madden MC,Shen Z,Kantrow SP

    更新日期:2019-09-16 00:00:00

  • 16α-Hydroxyestrone: Mass Spectrometry-Based Methodologies for the Identification of Covalent Adducts Formed with Blood Proteins.

    abstract::Elevated levels of the estrone metabolite, 16α-hydroxyestrone (16αOHE1), have been linked with multiple diseases. As an electrophilic reactive metabolite, covalent binding to proteins is thought to constitute one of the possible mechanisms in the onset of deleterious health outcomes associated with 16αOHE1. Whereas ma...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Charneira C,Nunes J,Antunes AMM

    更新日期:2020-08-17 00:00:00

  • Gut microbiome perturbations induced by bacterial infection affect arsenic biotransformation.

    abstract::Exposure to arsenic affects large human populations worldwide and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which ar...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lu K,Cable PH,Abo RP,Ru H,Graffam ME,Schlieper KA,Parry NM,Levine S,Bodnar WM,Wishnok JS,Styblo M,Swenberg JA,Fox JG,Tannenbaum SR

    更新日期:2013-12-16 00:00:00

  • Synthesis, Characterization, and Identification of New in Vitro Covalent DNA Adducts of Divinyl Sulfone, an Oxidative Metabolite of Sulfur Mustard.

    abstract::Divinyl sulfone (DVS) is an important oxidative metabolic product of sulfur mustard (SM) in vitro and in vivo. Although DVS is not a classical blister agent, its high reactivity and toxicity induced by vinyl groups can also cause blisters like SM upon contact with the skin, eyes, and respiratory organs. The purpose of...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lv S,Zhang Y,Xu B,Xu H,Zhao Y,Chen J,Gao Z,Wu J,Xie J

    更新日期:2017-10-16 00:00:00

  • Slow-binding inhibition of carboxylesterase and other serine hydrolases by chlorodifluoroacetaldehyde.

    abstract::The chlorofluorocarbon substitute 1,2-dichloro-1,1-difluoroethane (HCFC-132b) undergoes oxidative metabolism in rats to give a range of metabolites, including chlorodifluoroacetaldehyde [Harris and Anders (1991) Chem. Res. Toxicol. 4, 180]. The present experiments were undertaken after studies to characterize an unide...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Yin H,Jones JP,Anders MW

    更新日期:1993-09-01 00:00:00

  • Synthesis and characterization of DNA minor groove binding alkylating agents.

    abstract::Derivatives of methyl 3-(1-methyl-5-(1-methyl-5-(propylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl)-1H-pyrrol-3-ylamino)-3-oxopropane-1-sulfonate (1), a peptide-based DNA minor groove binding methylating agent, were synthesized and characterized. In all cases, the N-terminus was appended with an O-methyl sulfonate ester, while...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Iyer P,Srinivasan A,Singh SK,Mascara GP,Zayitova S,Sidone B,Fouquerel E,Svilar D,Sobol RW,Bobola MS,Silber JR,Gold B

    更新日期:2013-01-18 00:00:00

  • Potent mutagenicity of 3-methylindole requires pulmonary cytochrome P450-mediated bioactivation: a comparison to the prototype cigarette smoke mutagens B(a)P and NNK.

    abstract::3-Methylindole (3MI) is a preferential pneumotoxicant found in cigarette smoke. A number of lung-expressed human cytochrome P450 enzymes, including 1A1, 2F1, and 2A13, catalyze the metabolism of 3MI to reactive intermediates that fragment DNA, measured with the Comet assay to assess DNA damage, in a cytochrome P450-de...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Weems JM,Lamb JG,D'Agostino J,Ding X,Yost GS

    更新日期:2010-11-15 00:00:00

  • Glutathione adduct of methylmercury activates the Keap1-Nrf2 pathway in SH-SY5Y cells.

    abstract::Methylmercury (MeHg) reacts readily with GSH, leading to the formation of a MeHg-SG adduct that is excreted into extracellular space through multidrug-resistance-associated protein (MRP), which is regulated by the transcription factor Nrf2. We previously reported that MeHg covalently modifies Keap1 and activates Nrf2 ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Yoshida E,Abiko Y,Kumagai Y

    更新日期:2014-10-20 00:00:00

  • Flavokawains a and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice.

    abstract::Anxiolytic kava products have been associated with rare but severe hepatotoxicity in humans. This adverse potential has never been captured in animal models, and the responsible compound(s) remains to be determined. The lack of such knowledge greatly hinders the preparation of a safer kava product and limits its benef...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Narayanapillai SC,Leitzman P,O'Sullivan MG,Xing C

    更新日期:2014-10-20 00:00:00

  • Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization.

    abstract::Fragrances are common causes of contact allergy. Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an important fragrance terpene. It is considered a weak contact allergen and is used for fragrance allergy screening among consecutive dermatitis patients. Analogous to other monoterpenes studied, such as limonene and ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Hagvall L,Bäcktorp C,Svensson S,Nyman G,Börje A,Karlberg AT

    更新日期:2007-05-01 00:00:00

  • Synthesis of a hapten to be used in development of immunoassays for trans-3'-hydroxycotinine, a major metabolite of cotinine.

    abstract::4-Carboxyl-substituted analogues of trans-3'-hydroxycotinine were synthesized to be covalently linked to macromolecules for antibody production. 3-Pyridyl-N-methylnitrone was condensed with dimethyl fumarate to give two isomeric isoxazolidines. Hydrogenolysis of the major product [2RS-(2 alpha,3 alpha,3 beta)]-3-carbo...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Desai DH,Amin S

    更新日期:1991-09-01 00:00:00

  • Metabolomic characterization of laborers exposed to welding fumes.

    abstract::The complex composition of welding fumes, multiplicity of molecular targets, diverse cellular effects, and lifestyles associated with laborers vastly complicate the assessment of welding fume exposure. The urinary metabolomic profiles of 35 male welders and 16 male office workers at a Taiwanese shipyard were character...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Wang KC,Kuo CH,Tian TF,Tsai MH,Chiung YM,Hsiech CM,Tsai SJ,Wang SY,Tsai DM,Huang CC,Tseng YJ

    更新日期:2012-03-19 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


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

    更新日期:1999-11-01 00:00:00

  • Epoxide reduction to an alcohol: a novel metabolic pathway for perylene quinone-type alternaria mycotoxins in mammalian cells.

    abstract::The group of perylene quinone-type Alternaria toxins contains several congeners with epoxide groups, for example, altertoxin II (ATX II) and stemphyltoxin III (STTX III). Recent studies in our laboratory have disclosed that the epoxide moieties of ATX II and STTX III are reduced to alcohols in human colon Caco-2 cells...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Fleck SC,Pfeiffer E,Podlech J,Metzler M

    更新日期:2014-02-17 00:00:00

  • Identification of individual benzo[c]phenanthrene dihydrodiol epoxide-DNA adducts by the 32P-postlabeling assay.

    abstract::Purine deoxyribonucleoside 3'-phosphates were reacted separately with the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. Products resulting from the cis and trans opening of the epoxide ring by the exocyclic amino groups of deoxyadenosine and deoxyguanosine 3'-phosphates were separat...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Canella KA,Peltonen K,Yagi H,Jerina DM,Dipple A

    更新日期:1992-09-01 00:00:00

  • A Multiplatform Approach for the Discovery of Novel Drug-Induced Kidney Injury Biomarkers.

    abstract::Drug-induced kidney injury (DIKI) is a common toxicity observed in pharmaceutical development. We demonstrated the use of label-free liquid chromatography-mass spectrometry (LC-MS) and multiplex liquid chromatography-single reaction monitoring (LC-SRM) as practical extensions of standard immunoassay based safety bioma...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Chen L,Smith J,Mikl J,Fryer R,Pack F,Williams BJ,Phillips JA,Papov VV Jr

    更新日期:2017-10-16 00:00:00

  • Structure-toxicity relationships for the effects to Tetrahymena pyriformis of aliphatic, carbonyl-containing, alpha,beta-unsaturated chemicals.

    abstract::Toxicity data for 82 aliphatic chemicals with an alpha,beta-unsaturated substructure were compiled. Toxicity was assessed in the 2-day Tetrahymena pyriformis population growth impairment assay. Toxic potency [log(IGC50(-1))] for most of these chemicals was in excess of baseline narcosis as quantified by the 1-octanol/...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Schultz TW,Netzeva TI,Roberts DW,Cronin MT

    更新日期:2005-02-01 00:00:00

  • Chemical mechanisms for skin sensitization by aromatic compounds with hydroxy and amino groups.

    abstract::It is well-known that aromatic diamino-, dihydroxy-, and amino-hydroxy compounds, with NH(2) and OH groups in ortho- or para-positions relative to each other, are strong skin sensitizers. In this paper, we analyze published potency and cross-reactivity data, whereby animals sensitized to one of these compounds are cha...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Aptula AO,Enoch SJ,Roberts DW

    更新日期:2009-09-01 00:00:00

  • Genotoxicity of the hydroquinone metabolite of ochratoxin A: structure-activity relationships for covalent DNA adduction.

    abstract::Ochratoxin A (OTA) is a mycotoxin that shows potent nephrotoxicity and renal carcinogenicity in rodents. One hypothesis for OTA-induced tumor formation is based on its genotoxic properties that are promoted by oxidative metabolism. Like other chlorinated phenols, OTA undergoes an oxidative dechlorination process to ge...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Tozlovanu M,Faucet-Marquis V,Pfohl-Leszkowicz A,Manderville RA

    更新日期:2006-09-01 00:00:00

  • Kinetics of DNA Adducts and Abasic Site Formation in Tissues of Mice Treated with a Nitrogen Mustard.

    abstract::Nitrogen mustards (NM) are an important class of chemotherapeutic drugs used in the treatment of malignant tumors. The accepted mechanism of action of NM is through the alkylation of DNA bases. NM-adducts block DNA replication in cancer cells by forming cytotoxic DNA interstrand cross-links. We previously characterize...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Chen H,Cui Z,Hejazi L,Yao L,Walmsley SJ,Rizzo CJ,Turesky RJ

    更新日期:2020-04-20 00:00:00

  • Synthesis of the PhIP adduct of 2'-deoxyguanosine and its incorporation into oligomeric DNA.

    abstract::The 2'-deoxyguanosine adduct of the dietary mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been synthesized and incorporated into DNA using solid state synthesis technology. The key step to obtaining the C8-dG adduct is a palladium (Xantphos-chelated)-catalyzed N-arylation (Buchwald-Hartwig reactio...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Bonala R,Torres MC,Iden CR,Johnson F

    更新日期:2006-06-01 00:00:00

  • Isoflavones as Ah Receptor Agonists in Colon-Derived Cell Lines: Structure-Activity Relationships.

    abstract::Many of the protective responses observed for flavonoids in the gastrointestinal track resemble aryl hydrocarbon receptor (AhR)-mediated effects. Therefore, we examined the structure-activity relationships of isoflavones and isomeric flavone and flavanones as AhR ligands on the basis of their induction of CYP1A1, CYP1...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Park H,Jin UH,Orr AA,Echegaray SP,Davidson LA,Allred CD,Chapkin RS,Jayaraman A,Lee K,Tamamis P,Safe S

    更新日期:2019-11-18 00:00:00