当前位置： SCI文献检索 > CHEMICAL RESEARCH IN TOXICOLOGY期刊下所有文献 > Liquid chromatography electrospray-mass spectrometry of urinary aflatoxin biomarkers: characterization and application to dosimetry and chemoprevention in rats.

Liquid chromatography electrospray-mass spectrometry of urinary aflatoxin biomarkers: characterization and application to dosimetry and chemoprevention in rats.

Abstract：

:A liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) method for the measurement of aflatoxin biomarkers in urine has been developed and validated. The two major aflatoxin-DNA adducts formed in rat tissues, aflatoxin N(7)-guanine and its imidazole ring opened derivative, 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxy-aflatoxin B(1), were detected and quantified in urine by the LC-ESI-MS/MS technique. Other metabolites derived from the conjugation and/or oxidation of aflatoxin B(1) measured in the urine of dosed rats included aflatoxin P(1), aflatoxin P(1)-glucuronide, aflatoxin Q(1), aflatoxin M(1), 8,9-dihydro-8,9-dihydroxy aflatoxin B(1), aflatoxin B(1)-mercapturic acid, the aflatoxin-cysteine glycine adduct derived from the aflatoxin-glutathione conjugate, aflatoxin M(1)P(1) and the aflatoxin B(1)-dialcohol. For in vivo studies to determine the dosimetry of certain aflatoxin metabolites, aflatoxin B(2) was used as an internal standard for recovery since this compound is not naturally produced in rats. In the final method using the internal standard, the coefficient of variation of six replicate analyses of in vivo rat urine samples for aflatoxin N(7)-guanine, aflatoxin B(1)-mercapturic acid, and aflatoxin M(1) was 12.5, 12.8, and 5.8%, respectively. Further, the LC-ESI-MS/MS method to detect aflatoxin N(7)-guanine in in vivo rat urine samples was at least 20-fold more sensitive than prior techniques. Using the LC-ESI-MS/MS technique, the dosimetry, on a weekly basis, of major urinary aflatoxin metabolites was assessed in animals chronically dosed over a 5-week period. Of particular importance was the application of this method to determine the modulation of levels of urinary aflatoxin metabolites by treatment with oltipraz, a chemopreventive agent that can completely ablate aflatoxin hepatocarcinogenesis in the rat. After 1 week, oltipraz administration diminished urinary aflatoxin N(7)-guanine, aflatoxin B(1)-mercapturic acid and aflatoxin M(1) levels by 83, 92, and 82%, respectively. The magnitude of this reduction was persistent at the day 14, 21, 28, and 35-day time points with the average decrease of aflatoxin N(7)-guanine, aflatoxin B(1)-mercapturic acid and aflatoxin M(1) being 73, 92, and 90%, respectively. Importantly, even under circumstances where the oltipraz intervention was most efficient in reducing aflatoxin metabolite levels, the LC-ESI-MS/MS method was still sensitive enough to detect the reduced biomarker content. This outcome has important translational implications for the application and analysis of the efficacy of primary and secondary prevention interventions in human populations where ambient exposure levels are low, but the toxicologic hazards of these exposures remain high.

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Walton M,Egner P,Scholl PF,Walker J,Kensler TW,Groopman JD

doi

10.1021/tx010063a

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

919-26

issue

7

eissn

0893-228X

issn

1520-5010

pii

tx010063a

journal_volume

14

pub_type

杂志文章

相关文献

CHEMICAL RESEARCH IN TOXICOLOGY文献大全
  • Identification of 14 quercetin phase II mono- and mixed conjugates and their formation by rat and human phase II in vitro model systems.

    abstract：:In this study, the HPLC, UV-vis, LC-MS, and 1H NMR characteristics of 14 different phase II mono- and mixed conjugates of quercetin were determined, providing a useful tool in the identification of quercetin phase II metabolite patterns in various biological systems. Using these data, the phase II metabolism of querce...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049826v

    authors： van der Woude H,Boersma MG,Vervoort J,Rietjens IM

    更新日期：2004-11-01 00:00:00

  • Unveiling the Variability of "Quartz Hazard" in Light of Recent Toxicological Findings.

    abstract：:The variability of quartz hazard stands as one of the most puzzling issues in particle toxicology, notwithstanding the fact that silicosis, the most ancient occupational disease, was the very topic from which the study of the toxicity of particulates developed. Over the years, other adverse effects of silica particles...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.6b00409

    authors： Pavan C,Fubini B

    更新日期：2017-01-17 00:00:00

  • Characterization of the transient oxaphosphetane BChE inhibitor formed from spontaneously activated ethephon.

    abstract：:The major plant growth regulator ethephon degrades to ethylene and phosphate in aqueous solutions and plants and is spontaneously activated to a butyrylcholinesterase (BChE) inhibitor in alkaline solutions and animal tissues. In the present (31)P NMR kinetic study of the reactions of ethephon in pH 7.4 carbonate buffe...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx4002429

    authors： Lantz SR,Casida JE

    更新日期：2013-09-16 00:00:00

  • Structure-activity models for contact sensitization.

    abstract：:Allergic contact dermatitis (ACD) is a widespread cause of workers' disabilities. Although some substances found in the workplace are rigorously tested, the potential of the vast majority of chemicals to cause skin sensitization remains unknown. At the same time, exhaustive testing of all chemicals in workplaces is co...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx0497806

    authors： Fedorowicz A,Singh H,Soderholm S,Demchuk E

    更新日期：2005-06-01 00:00:00

  • Identification of protein targets of 4-hydroxynonenal using click chemistry for ex vivo biotinylation of azido and alkynyl derivatives.

    abstract：:Polyunsaturated fatty acids (PUFA) are primary targets of free radical damage during oxidative stress. Diffusible electrophilic alpha,beta-unsaturated aldehydes, such as 4-hydroxynonenal (HNE), have been shown to modify proteins that mediate cell signaling (e.g., IKK and Keap1) and alter gene expression pathways respo...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx700347w

    authors： Vila A,Tallman KA,Jacobs AT,Liebler DC,Porter NA,Marnett LJ

    更新日期：2008-02-01 00:00:00

  • Reductive activation of mitomycin C by thiols: kinetics, mechanism, and biological implications.

    abstract：:The clinically used antitumor antibiotic mitomycin C requires a reductive activation to be converted to a bis-electrophile that forms several covalent adducts with DNA, including an interstrand cross-link which is considered to be the lesion responsible for the cytotoxic effects of the drug. Enzymes such as cytochrome...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx9002758

    authors： Paz MM

    更新日期：2009-10-01 00:00:00

  • A novel method for the isolation and identification of stable DNA adducts formed by Dibenzo[a,l]pyrene and Dibenzo[a,l]pyrene 11, 12-dihydrodiol 13,14-epoxides in vitro.

    abstract：:Our laboratory previously reported the identification and quantification of depurinating DNA adducts of dibenzo[a,l]pyrene (DB[a,l]P) in vitro, which comprise about 84% of all the DNA adducts that are formed [Li, K.-M., et al. (1995) Biochemistry 34, 8043-8049]. To determine a complete adduct profile and identify both...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx980203p

    authors： Devanesan P,Ariese F,Jankowiak R,Small GJ,Rogan EG,Cavalieri EL

    更新日期：1999-09-01 00:00:00

  • Effect of human glutathione S-transferases on glutathione-dependent inactivation of cytochrome P450-dependent reactive intermediates of diclofenac.

    abstract：:Idiosyncratic adverse drug reactions due to the anti-inflammatory drug diclofenac have been proposed to be caused by the generation of reactive acyl glucuronides and oxidative metabolites. For the oxidative metabolism of diclofenac by cytochromes P450 at least five different reactive intermediates have been proposed p...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx400204d

    authors： Dragovic S,Boerma JS,Vermeulen NP,Commandeur JN

    更新日期：2013-11-18 00:00:00

  • Mutagenic bypass of 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) by DNA polymerase κ in human cells.

    abstract：:The formation of 8-oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) in DNA and in the nucleotide pool results in G:C→T:A and A:T→C:G substitution mutations, respectively, since G(O) can pair with both C and A. In this study, the role of DNA polymerase κ in the mutagenicity of G(O) was investigated, using a supF shuttle...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx300259x

    authors： Kamiya H,Kurokawa M

    更新日期：2012-08-20 00:00:00

  • Identification of antrocin from Antrodia camphorata as a selective and novel class of small molecule inhibitor of Akt/mTOR signaling in metastatic breast cancer MDA-MB-231 cells.

    abstract：:The PI3K/Akt/mTOR pathway is considered to be an attractive target for the development of novel anticancer molecules. This paper reports for the first time that a small molecule, antrocin (MW = 234), from Antrodia camphorata was a potent antagonist in various cancer types, being highest in metastatic breast cancer MDA...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx100318m

    authors： Rao YK,Wu AT,Geethangili M,Huang MT,Chao WJ,Wu CH,Deng WP,Yeh CT,Tzeng YM

    更新日期：2011-02-18 00:00:00

  • Identification and Profiling of Environmental Chemicals That Inhibit the TGFβ/SMAD Signaling Pathway.

    abstract：:The transforming growth factor beta (TGFβ) superfamily of secreted signaling molecules and their cognate receptors regulate cell fate and behaviors relevant to many developmental and disease processes. Disruption of TGFβ signaling during embryonic development can, for example, affect morphogenesis and differentiation ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00228

    authors： Wei Z,Sakamuru S,Zhang L,Zhao J,Huang R,Kleinstreuer NC,Chen Y,Shu Y,Knudsen TB,Xia M

    更新日期：2019-12-16 00:00:00

  • Internalization of carbon black and maghemite iron oxide nanoparticle mixtures leads to oxidant production.

    abstract：:The risk of potential human exposure to mixed nanomaterials in consumer, occupational, and medicinal settings is increasing as nanomaterials enter both the workplace and the marketplace. In this study, we investigated the toxicity of mixed engineered carbon black (ECB) and maghemite iron oxide (Fe(2)O(3)) nanoparticle...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx100307h

    authors： Berg JM,Ho S,Hwang W,Zebda R,Cummins K,Soriaga MP,Taylor R,Guo B,Sayes CM

    更新日期：2010-12-20 00:00:00

  • Mechanism of formation of ethenoguanine adducts from 2-haloacetaldehydes: 13C-labeling patterns with 2-bromoacetaldehyde.

    abstract：:The mechanism of formation of etheno (epsilon) adducts of nucleic acid bases from 2-haloacetaldehydes is generally assumed to occur via initial Schiff base formation resulting from reaction of the aldehyde with an exocyclic amine. We recently revised the 1H NMR assignments of the epsilon protons of 1,N2-epsilon-Guo (G...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00038a014

    authors： Guengerich FP,Persmark M

    更新日期：1994-03-01 00:00:00

  • Quantitation of 7-ethylguanine in leukocyte DNA from smokers and nonsmokers by liquid chromatography-nanoelectrospray-high resolution tandem mass spectrometry.

    abstract：:There is considerable evidence for the exposure of humans to an unknown ethylating agent, and some studies indicate that cigarette smoking may be one source of this exposure. Therefore, we have developed a liquid chromatography-nanoelectrospray-high resolution tandem mass spectrometry-selected reaction monitoring (LC-...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx200262d

    authors： Balbo S,Villalta PW,Hecht SS

    更新日期：2011-10-17 00:00:00

  • In vitro DNA deamination by alpha-nitrosaminoaldehydes determined by GC/MS-SIM quantitation.

    abstract：:The deamination of DNA bases by three alpha-nitrosaminoaldehydes, butylethanalnitrosamine, methylethanalnitrosamine, and N-nitroso-2-hydroxymorpholine (NHMOR), the direct metabolite of potent animal carcinogen N-nitrosodiethanolamine, was demonstrated by a set of in vitro experiments. The deamination of guanine, adeni...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx990126d

    authors： Park M,Loeppky RN

    更新日期：2000-02-01 00:00:00

  • Metabolism and mutagenicity of dibenzo[a,e]pyrene and the very potent environmental carcinogen dibenzo[a,l]pyrene.

    abstract：:Dibenzo[a,l]pyrene (DB[a,l]P) is one of the most potent carcinogens ever tested in mouse skin and rat mammary gland. DB[a,l]P is present in cigarette smoke and, presumably, in other environmental pollutants. Metabolism and mutagenicity studies of this compound compared to the weak carcinogen dibenzo[a,e]pyrene (DB[a,e...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00018a014

    authors： Devanesan PD,Cremonesi P,Nunnally JE,Rogan EG,Cavalieri EL

    更新日期：1990-11-01 00:00:00

  • Metabolic Profiles of Tetrabromobisphenol A in Humans Extrapolated from Humanized-Liver Mouse Data Using a Simplified Physiologically Based Pharmacokinetic Model.

    abstract：:Tetrabromobisphenol A, a brominated flame retardant, is increasingly prevalent worldwide and presents a potential health risk. Adjusted animal biomonitoring equivalents of tetrabromobisphenol A after orally administered doses in humanized-liver mice were scaled up to humans using known species allometric scaling facto...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.0c00358

    authors： Miura T,Uehara S,Shigeta K,Yoshizawa M,Kamiya Y,Murayama N,Shimizu M,Suemizu H,Yamazaki H

    更新日期：2020-11-16 00:00:00

  • Identification and characterization of thiosemicarbazones with antifungal and antitumor effects: cellular iron chelation mediating cytotoxic activity.

    abstract：:Thiosemicarbazones derived from acetylpyrazines were prepared by condensing an acetylpyrazine or a ring-substituted acetylpyrazine with thiosemicarbazide. Using the same procedure, N, N-dimethylthiosemicarbazones were synthesized from acetylpyrazines and N, N-dimethylthiosemicarbazide. A total of 20 compounds (16 nove...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx800182k

    authors： Opletalová V,Kalinowski DS,Vejsová M,Kunes J,Pour M,Jampílek J,Buchta V,Richardson DR

    更新日期：2008-09-01 00:00:00

  • Virtual Cross-Linking of the Active Nemorubicin Metabolite PNU-159682 to Double-Stranded DNA.

    abstract：:The DNA alkylating mechanism of PNU-159682 (PNU), a highly potent metabolite of the anthracycline nemorubicin, was investigated by gel-electrophoretic, HPLC-UV, and micro-HPLC/mass spectrometry (MS) measurements. PNU quickly reacted with double-stranded oligonucleotides, but not with single-stranded sequences, to form...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.6b00362

    authors： Scalabrin M,Quintieri L,Palumbo M,Riccardi Sirtori F,Gatto B

    更新日期：2017-02-20 00:00:00

  • Role of P450 1A1 and P450 1A2 in bioactivation versus detoxication of the renal carcinogen aristolochic acid I: studies in Cyp1a1-/-, Cyp1a2-/-, and Cyp1a1/1a2-/- mice.

    abstract：:Exposure to aristolochic acid I (AAI) is associated with aristolochic acid nephropathy, Balkan endemic nephropathy, and urothelial cancer. Individual differences in xenobiotic-metabolizing enzyme activities are likely to be a reason for interindividual susceptibility to AA-induced disease. We evaluated the reductive a...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx200259y

    authors： Arlt VM,Levová K,Bárta F,Shi Z,Evans JD,Frei E,Schmeiser HH,Nebert DW,Phillips DH,Stiborová M

    更新日期：2011-10-17 00:00:00

  • Hydrolytic Cleavage Products of Globin Adducts in Urine as Possible Biomarkers of Cumulative Dose: Proof of Concept Using Styrene Oxide as a Model Adduct-Forming Compound.

    abstract：:A new experimental model was designed to study the fate of globin adducts with styrene 7,8-oxide (SO), a metabolic intermediate of styrene and a model electrophilic compound. Rat erythrocytes were incubated with SO at 7 or 22 °C. Levels of specific amino acid adducts in globin were determined by LC/MS analysis of the ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.5b00518

    authors： Mráz J,Hanzlíková I,Moulisová A,Dušková Š,Hejl K,Bednářová A,Dabrowská L,Linhart I

    更新日期：2016-04-18 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

  • Identification of drug-induced myocardial infarction-related protein targets through the prediction of drug-target interactions and analysis of biological processes.

    abstract：:Drug-induced myocardial infarction (DIMI) is one of the most serious adverse drug effects that often lead to death. Therefore, the identification of DIMI at the early stages of drug development is essential. For this purpose, the in vitro testing and in silico prediction of interactions between drug-like substances an...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx500147d

    authors： Ivanov SM,Lagunin AA,Pogodin PV,Filimonov DA,Poroikov VV

    更新日期：2014-07-21 00:00:00

  • Metabolites and safety: What are the concerns, and how should we address them?

    abstract：:The issue of the safety of drug metabolites in humans is a complex one. In this commentary, a proposal is made regarding how to deal with drug metabolites observed in humans such that the safety of these molecules can be assured. The human radiolabeled ADME study, in which metabolites are identified and quantified in ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx0602012

    authors： Smith DA,Obach RS

    更新日期：2006-12-01 00:00:00

  • Ferroptosis: The Greasy Side of Cell Death.

    abstract：:Ferroptosis is a form of cell death that requires phospholipid peroxidation and has attracted increased attention, both as a means to eradicate tumors resistant to standard chemotherapy and for its potential contribution to tissue damage such as in ischemia/reperfusion. The center stage taken by phospholipid peroxidat...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章,评审

    doi：10.1021/acs.chemrestox.8b00349

    authors： Friedmann Angeli JP,Miyamoto S,Schulze A

    更新日期：2019-03-18 00:00:00

  • Bioactivation of the selective estrogen receptor modulator desmethylated arzoxifene to quinoids: 4'-fluoro substitution prevents quinoid formation.

    abstract：:Although selective estrogen receptor modulators (SERMs) are useful in the treatment and prevention of breast cancer, the SERM tamoxifen has been associated with an increased risk of endometrial cancer possibly due to metabolism to electrophilic quinoids. Another SERM, arzoxifene is currently in clinical trials for the...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049776u

    authors： Liu H,Liu J,van Breemen RB,Thatcher GR,Bolton JL

    更新日期：2005-02-01 00:00:00

  • Synthesis and sequence-specific DNA binding of a topoisomerase inhibitory analog of Hoechst 33258 designed for altered base and sequence recognition.

    abstract：:The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. In...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00029a003

    authors： Singh MP,Joseph T,Kumar S,Bathini Y,Lown JW

    更新日期：1992-09-01 00:00:00

  • Enzyme induction by L-buthionine (S,R)-sulfoximine in cultured mouse hepatoma cells.

    abstract：:Induction of Phase II enzymes of the [Ah] gene battery by L-buthionine (S,R)-sulfoximine (BSO) and other agents was examined in mouse hepatoma Hepa-1c1c7 cells. BSO, a nonelectrophilic inhibitor of gamma-glutamylcysteine synthetase (GCS), is routinely used to examine the toxicological implications of GSH depletion. Ex...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00045a015

    authors： Shertzer HG,Vasiliou V,Liu RM,Tabor MW,Nebert DW

    更新日期：1995-04-01 00:00:00

  • Titanium nanoparticle inhalation induces renal fibrosis in mice via an oxidative stress upregulated transforming growth factor-β pathway.

    abstract：:Titanium dioxide nanoparticles (Nano-TiO2) are gradually being used extensively in clinical settings, industry, and daily life. Accumulation studies showed that Nano-TiO2 exposure is able to cause injuries in various animal organs, including the lung, liver, spleen, and kidney. However, it remains unclear whether expo...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx500287f

    authors： Huang KT,Wu CT,Huang KH,Lin WC,Chen CM,Guan SS,Chiang CK,Liu SH

    更新日期：2015-03-16 00:00:00

  • Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1.

    abstract：:The hepatic carcinogen aflatoxin B1 (AFB1) is metabolized in the liver by at least four different P450s, all of which exhibit large interindividual differences in the expression levels. These differences could affect the individual risk of hepatocellular carcinoma (HCC). We investigated the metabolism of AFB1 in a pan...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx050358e

    authors： Kamdem LK,Meineke I,Gödtel-Armbrust U,Brockmöller J,Wojnowski L

    更新日期：2006-04-01 00:00:00