Abstract:
:Furan has been found in a number of heated food items and is carcinogenic in the liver of rats and mice. Estimates of human exposure on the basis of concentrations measured in food are not reliable because of the volatility of furan. A biomarker approach is therefore indicated. We searched for metabolites excreted in the urine of male Fischer 344 rats treated by oral gavage with 40 mg of furan per kg of body weight. A control group received the vehicle oil only. Urine collected over two 24-h periods both before and after treatment was analyzed by a column-switching LC-MS/MS method. Data were acquired by a full scan survey scan in combination with information dependent acquisition of fragmentation spectra by the use of a linear ion trap. Areas of 449 peaks were extracted from the chromatograms and used for principal component analysis (PCA). The first principal component fully separated the samples of treated rats from the controls in the first post-treatment sampling period. Thirteen potential biomarkers selected from the corresponding loadings plot were reanalyzed using specific transitions in the MRM mode. Seven peaks that increased significantly upon treatment were further investigated as biomarkers of exposure. MS/MS information indicated conjugation with glutathione on the basis of the characteristic neutral loss of 129 for mercapturates. Adducts with the side chain amino group of lysine were characterized by a neutral loss of 171 for N-acetyl- l-lysine. Analysis of products of in vitro incubations of the reactive furan metabolite cis-2-butene-1,4-dial with the respective amino acid derivatives supported five structures, including a new 3-methylthio-pyrrole metabolite probably formed by beta-lyase reaction on a glutathione conjugate, followed by methylation of the thiol group. Our results demonstrate the potential of comprehensive mass spectrometric analysis of urine combined with multivariate analyses for metabolic profiling in search of biomarkers of exposure.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Kellert M,Wagner S,Lutz U,Lutz WKdoi
10.1021/tx7004212subject
Has Abstractpub_date
2008-03-01 00:00:00pages
761-8issue
3eissn
0893-228Xissn
1520-5010journal_volume
21pub_type
杂志文章abstract::In May 1981, a massive food-borne intoxication occurred in Spain. The so-called toxic oil syndrome (TOS) was associated with the consumption of aniline-denatured and refined rapeseed oil that was illegally sold as edible olive oil. Fatty acid anilides and fatty acid derivatives of 3-(phenylamino)propane-1,2-diol were ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx990105j
更新日期:1999-12-01 00:00:00
abstract::Guidance from the Food and Drug Administration on drug interaction studies does not include a specific section on contributions of metabolites to observed inhibitory drug-drug interactions, and the quantitative role of drug metabolites in inhibitory drug-drug interactions is not presently known. The current work was u...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx800491e
更新日期:2009-02-01 00:00:00
abstract::3,N4-Etheno-2'-deoxycytidine, 3-(hydroxyethyl)-2'-deoxyuridine, and 3,N4-ethano-2'-deoxy-cytidine are found in DNA of cells treated with either vinyl chloride or 1,3-bis(2-chloroethyl)-nitrosourea. These exocyclic and related DNA adducts were incorporated into oligodeoxynucleotides, which were then used as templates f...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00043a021
更新日期:1995-01-01 00:00:00
abstract::Studies on the metabolic bioactivation of the psychotomimetic amine phencyclidine have been pursued through the characterization of a new metabolite which is formed via initial cytochrome P-450 catalyzed oxidation of the parent drug to the corresponding iminium species. CI mass spectrometric and diode array UV and 1H ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00002a007
更新日期:1988-03-01 00:00:00
abstract::It is vital that methylated trivalent arsenicals [MA(III) and DMA(III)] are described and characterized unequivocally due to their high toxicity. Two different ways of generating the methylated trivalent arsenicals have been practiced-reduction of the methylated pentavalent arsenical either by the sodium-metabisulfite...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049978q
更新日期:2004-08-01 00:00:00
abstract::The nuclear receptor human pregnane X receptor (hPXR) is a ligand-regulated transcription factor that responds to a wide range of endogenous and xenobiotic molecules. Upon activation with ligands, hPXR can increase induction levels of metabolic enzymes. Therefore, hPXR plays a critical role in drug metabolism and excr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200310j
更新日期:2011-10-17 00:00:00
abstract::Bisphenol A (BPA) is ubiquitous in the environment and is reported to be present at high concentrations in placental tissue, where its presence raises concerns over its potential to disrupt placental function. This report investigates how BPA interferes with the survival of human choriocarcinoma BeWo cells (a model of...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00093
更新日期:2015-09-21 00:00:00
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
更新日期:2006-12-01 00:00:00
abstract::The 1-octanol/water partition coefficients of a number of toxic and nontoxic analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were determined using centrifugal partition chromatography (CPC), a novel and effective technique for measuring lipophilicity, and found to be highly correlated with values calc...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00027a008
更新日期:1992-05-01 00:00:00
abstract::Raloxifene (Evista) is a second generation selective estrogen receptor modulator used in the treatment of osteoporosis and for chemoprevention of breast cancer. It is bioactivated to reactive intermediates, which covalently bind to proteins and form GSH conjugates upon incubation with NADPH and GSH-supplemented human ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800323w
更新日期:2008-12-01 00:00:00
abstract::8-Aminoguanine had previously been identified as one of the nucleic acid base modifications produced in livers of rats by treatment with the hepatocarcinogen 2-nitropropane (2-NP), and a hypothetical mechanism of activation of 2-NP to hydroxylamine-O-sulfonate or acetate that would lead to NH2+, an aminating species, ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00039a011
更新日期:1994-05-01 00:00:00
abstract::The reaction of sodium nitroprusside (SNP) with deoxyhemoglobin (Hb) results in two distinct EPR-detectable species, the one-electron-reduced nitroprusside ion [(CN)5FeNO]3- and nitrosylhemoglobin (HbNO). In the presence of excess cyanide (CN-) only the signal for [(CN)5FeNO]3- is observed. Thus, while free CN- does n...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00013a012
更新日期:1990-01-01 00:00:00
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
更新日期:2019-03-18 00:00:00
abstract::Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur t...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx9902082
更新日期:2000-03-01 00:00:00
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
更新日期:2004-11-01 00:00:00
abstract::Sudoxicam and meloxicam are nonsteroidal anti-inflammatory drugs (NSAIDs) from the enol-carboxamide class. While the only structural difference between the two NSAIDs is the presence of a methyl group on the C5-position of the 2-carboxamidothiazole motif in meloxicam, a marked difference in their toxicological profile...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800185b
更新日期:2008-09-01 00:00:00
abstract::All living organisms are exposed to xenobiotics from the environment. The exposure can lead to the formation of covalent adducts of xenobiotics or their metabolites with nucleic acids (NAs).The knowledge of NA adduct structure provides valuable information n the mechanism of carcinogenesis on a molecular level. While ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx5004535
更新日期:2015-02-16 00:00:00
abstract::Covalent binding of drug reactive metabolites to neutrophils or their precursors is thought to play a role in the development of drug-induced agranulocytosis. In this study, we used immunochemical techniques to compare the covalent binding of clozapine, vesnarinone, and procainamide (three drugs associated with agranu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050095o
更新日期:2005-09-01 00:00:00
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
更新日期:2008-09-01 00:00:00
abstract::Two 2-aminofluorene-derived hydroxamic acids that differ only in the nature of the N-acyl group were examined for their relative abilities to undergo covalent binding to nucleic acids. Studies of the bioactivation of N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) and N-hydroxy-N-glycolyl-2-aminofluorene (N-OH-GAF) were...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00001a008
更新日期:1988-01-01 00:00:00
abstract::Mouse models are powerful tools to study the developmental neurotoxicity of polychlorinated biphenyls (PCBs); however, studies of the oxidation of chiral PCB congeners to potentially neurotoxic hydroxylated metabolites (OH-PCBs) in mice have not been reported. Here, we investigate the atropselective oxidation of chira...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400229e
更新日期:2013-11-18 00:00:00
abstract::The conjugation of reactive drug metabolites to GSH is considered an important detoxification mechanism that can be spontaneous and/or mediated by glutathione S-transferases (GSTs). In case GSTs play an important role in GSH conjugation, genetically determined deficiencies in GSTs may be a risk factor for adverse drug...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100131f
更新日期:2010-09-20 00:00:00
abstract::Adverse events resulting from drug therapy can be a cause of drug withdrawal, reduced and or restricted clinical use, as well as a major economic burden for society. To increase the safety of new drugs, there is a need to better understand the mechanisms causing the adverse events. One way to derive new mechanistic hy...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00159
更新日期:2018-11-19 00:00:00
abstract::Metabolic pathways of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) remain incompletely characterized in humans. In this study, the metabolism of MeIQx was investigated in primary human hepatocytes. Six metabolites were characterized by UV and mass spectroscopy. Novel metabolites were additionally ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000176e
更新日期:2001-02-01 00:00:00
abstract::The hepatic metabolism of microcystins (MCs), potent cyclic peptide hepatotoxins produced by cyanobacteria, was studied by i.p. injection in mice and rats. An immunoaffinity purification method using an anti-MC-LR monoclonal antibody showed a remarkable effect on the removal of contaminants in the hepatic cytosol and ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960085a
更新日期:1996-12-01 00:00:00
abstract::A series of (alkylthio)trifluoropropanones containing a heterocyclic moiety was synthesized. The compounds were tested for in vitro inhibition of four hydrolytic enzymes including insect juvenile hormone esterase (JHE), eel acetylcholinesterase (AChE), yeast lipase (LP), and bovine alpha-chymotrypsin. The I50 values r...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00016a009
更新日期:1990-07-01 00:00:00
abstract::Deoxynivalenol (DON) is a trichothecene mycotoxin that is produced by several species of Fusarium, which may infect grain crops. DON, as well as other type-B trichothecenes, contain an α,β-unsaturated carbonyl group that may react with sulfhydryl groups in, for example, amino acids and peptides. Such conjugates have b...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00385
更新日期:2020-02-17 00:00:00
abstract::The reaction of the alpha, beta-unsaturated ketones methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) with nucleosides and 5'-mononucleotides was studied. The genotoxic activity of MVK and EVK in the SOS Chromotest was investigated. Three different types of adducts with deoxyguanosine were found and their structu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00019a007
更新日期:1991-01-01 00:00:00
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
更新日期:1999-09-01 00:00:00
abstract::2-(Glutathion-S-yl)-1,4-benzoquinone was found to be remarkably unstable in phosphate buffer (pH 7.4) even in the absence of oxygen. Intramolecular addition of the alpha-amino group of the glutamate residue to the quinone ring yielded ultimately 2,3-(glutathion-N, S-yl)-1,4-benzoquinone and 2,6-(glutathion-N,S-yl)-1,4...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9800699
更新日期:1998-10-01 00:00:00