Abstract:
:Glyoxal is generated endogenously from the degradation of glucose and the oxidation of carbohydrates, lipids, and the 2-deoxyribose moieties of DNA. Glyoxal is also widely used in industry and is present in cigarette smoke and food. Glyoxal can conjugate with nucleobases and proteins to give advanced glycation end products. N(2)-Carboxymethyl-2'-deoxyguanosine (N(2)-CMdG) and the cyclic 1,N(2)-glyoxal-dG are the major glyoxal adducts formed in DNA. In this study, we first assessed the stabilities of these two adducts. It turned out that 1,N(2)-glyoxal-dG was very unstable, with more than 70% of the adduct being decomposed to dG upon a 24 h incubation at 37 degrees C in phosphate-buffered saline. However, N(2)-CMdG was very stable; less than 0.5% of the lesion was degraded to dG after a 7 day incubation under the same conditions. We further developed a sensitive capillary liquid chromatography-electrospray ionization-tandem mass spectrometry coupled with a stable isotope dilution method and quantified the formation of N(2)-CMdG in calf thymus DNA and 293T human kidney epithelial cells that were exposed to glyoxal and in calf thymus DNA treated with d-glucose. Our results showed that N(2)-CMdG was produced at 2-134 lesions per 10(6) nucleosides in calf thymus DNA when the surrounding glyoxal concentration was increased from 10 to 500 microM and approximately 3-27 lesions per 10(7) nucleosides, while the D-glucose concentration changed from 2 to 50 mM. Furthermore, N(2)-CMdG was induced endogenously in 293T human kidney epithelial cells and exposure to glyoxal further stimulated the formation of this lesion; the level of this adduct ranged from 7 to 15 lesions per 10(8) nucleosides, while the glyoxal concentration increased from 10 microM to 1.25 mM. Collectively, our results suggested that N(2)-CMdG might serve as a biomarker for glyoxal exposure.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Wang H,Cao H,Wang Ydoi
10.1021/tx900286csubject
Has Abstractpub_date
2010-01-01 00:00:00pages
74-81issue
1eissn
0893-228Xissn
1520-5010journal_volume
23pub_type
杂志文章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::DNA damage and mutations are a major primary cause of cancer. Chemical bombardment of DNA is a major contributor to DNA damage. The Division of Chemical Toxicology recently hosted a panel of researchers who provided updates on the field of chemical toxicology at the nexus of DNA damage and repair. ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00438
更新日期:2021-01-28 00:00:00
abstract::The mechanism of DNA adduct formation by acroleins substituted with good leaving groups in the beta-position was investigated using [3-2H]-3-(p-nitrophenoxy)acrolein (1). Reaction of 1 with guanosine at acidic pH produced 9-beta-D-ribofuranosylpyrimido[1,2-alpha]purin-10(3H)-one containing equal amounts of deuterium a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx950105t
更新日期:1996-01-01 00:00:00
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
更新日期:2006-09-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly population, above 65 years of age. Multiple lines of evidence confirm the central role of 40-42 residue Abeta peptides in the pathogenesis of AD, but exact mechanisms of Abeta toxicity remain unclear. Recently, evidence has accumulat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900358j
更新日期:2010-02-15 00:00:00
abstract::We have previously reported that the diuretic thiosteroid spironolactone (SPL) inactivates rat liver microsomal cytochromes P450 [P450 (P450 3A and P450 2C11)] in a in a mechanism-based fashion, and we have identified two polar SPL metabolites (SPL-sulfinic acid and -sulfonic acid), formed in a partition ratio of appr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00024a012
更新日期:1991-11-01 00:00:00
abstract::Divicine is an unstable aglycon metabolite of the fava bean pyrimidine beta-glucoside vicine. Divicine has long been thought to be a mediator of an acute hemolytic crisis, known as favism, in susceptible individuals who ingest fava beans (Vicia faba). However, a recent report has questioned the chemical identity of th...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00034a009
更新日期:1993-07-01 00:00:00
abstract::The recent guidance on "Safety Testing of Drug Metabolites" issued by the U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER) has highlighted the importance of identifying and characterizing drug metabolites as early as possible in drug discovery and development. Furthermore, upon identif...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8003328
更新日期:2009-02-01 00:00:00
abstract::Epidemiologic studies have shown causal relationships between air pollution particles and adverse health effects in susceptible subpopulations. Fly ash particles (containing water-soluble and insoluble metals) are a component of ambient air particulate pollution and may contribute to particulate-induced health effects...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000110j
更新日期:2000-10-01 00:00:00
abstract::A well-defined silica nanoparticle model system was developed to study the effect of the size and structure of aggregates on their membranolytic activity. The aggregates were stable and characterized using transmission electron microscopy, dynamic light scattering, nitrogen adsorption, small-angle X-ray scattering, in...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2002178
更新日期:2011-11-21 00:00:00
abstract::DNA oxidation damage has been regarded as one of the possible mechanisms for the hepatic carcinogenesis of dioxin-like compounds (DLCs). In this study, we evaluated the toxic equivalency factor (TEF) from the standpoint of induced DNA oxidation products and their relationship to toxicity and carcinogenicity. Nine DNA ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00368
更新日期:2017-03-20 00:00:00
abstract::The activation of phospholipase A2 (PLA2) by lipid ozonation products is reported. The principal products from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) are 1-palmitoyl-2-[8-[3(5-octyl-1,2,4-trioxolan-3-yl)octanoyl]--sn-gly cero-3- phosphocholine (PC-Criegee ozonide) and 1-palmitoyl-2-(9...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00039a026
更新日期:1994-05-01 00:00:00
abstract::Exposure of individual histone proteins (H1, H2A, H2B, H3, or H4) and histone octamers (consisting of two molecules each of H2A, H2B, H3, and H4) to hydroxyl radicals, generated by gamma-irradiation, in the presence of O(2) generates protein-bound hydroperoxides in a dose-dependent fashion; this is in accord with prev...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000053u
更新日期:2000-07-01 00:00:00
abstract::Cytochrome P-450 enzymes have been postulated to oxidize amines through a variety of mechanisms. One of the means of distinguishing among potential pathways involves the use of kinetic hydrogen isotope effects: low isotope effects are characteristic of aminium radical mechanisms while high values are consistent with h...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00013a004
更新日期:1990-01-01 00:00:00
abstract::Thioredoxin reductase (TR), an NADPH-dependent flavoenzyme that catalyzes the reduction of many disulfide-containing substrates, plays an important role in the cellular response to oxidative stress. Trivalent arsenicals, especially methyl As that contains trivalent arsenic (MAs(III)), are potent noncompetitive inhibit...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0001878
更新日期:2001-03-01 00:00:00
abstract::Smoked cigarettes are the most prevalent form of litter worldwide, often finding their way into oceans and inland waterways. Cigarette smoke contains more than 4000 individual chemicals, some of them carcinogenic or otherwise toxic. We examined the cytotoxicity, genotoxicity, aryl hydrocarbon receptor (AhR), estrogen ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00201
更新日期:2019-08-19 00:00:00
abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed during the cooking of meats. PhIP is a potential human carcinogen: it undergoes metabolic activation to form electrophilic metabolites that bind to DNA and proteins, including serum albumin (SA). The structures of Ph...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300253j
更新日期:2012-10-15 00:00:00
abstract::Organochlorine (OC) compounds are some of the main toxicants present in the food web and target several cellular systems including the nonspecific immune system. The objective of this study was to test the hypothesis that OC compounds that activate neutrophils share common structural features. Using activation of phos...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0155449
更新日期:2002-02-01 00:00:00
abstract::Allyl alcohol (AA) is one of the environmental pollutants used as a herbicide and industrial chemical. AA undergoes enzymatic oxidation in vivo to form Acrolein (Acr), a highly reactive and ubiquitous environmental toxicant. The exposure to AA/Acr has detrimental effects on cells and is highly fatal. In corroboration ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00071
更新日期:2015-06-15 00:00:00
abstract::We have reassigned relative and absolute configurations by unambiguous stereoselective syntheses of the cis- (13s and 13R) and trans-N6-deoxyadenosine (dAdo) adduct diastereomers (14S and 14R) derived from (+/-)-11beta,12alpha-dihydroxy-13alpha,14alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]P DE-2), pr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800268f
更新日期:2008-12-01 00:00:00
abstract::beta-Carotene and other carotenoids are thought to exert disease preventive actions by scavenging reactive free radicals, but the mechanisms of these reactions are poorly understood. We detected products formed by reaction of beta-carotene with alkoxyl, and alkylperoxyl free radicals generated by thermolysis of azobis...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx950151t
更新日期:1996-01-01 00:00:00
abstract::Diethylstilbestrol (DES) and hexestrol (HES) are carcinogenic synthetic estrogens. The major metabolites of these compounds are their catechol derivatives, 3'-OH-DES and 3'-OH-HES. Oxidation of these metabolites leads to the electrophilic quinones, which are presumably involved in the tumor-initiating process. A synth...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970140v
更新日期:1998-05-01 00:00:00
abstract::4-Hydroxy-2-nonenal (HNE), a major electrophilic byproduct of lipid peroxidation, is mutagenic and cytotoxic. The two pairs of HNE-derived diastereomeric 1,N2-propanodeoxyguanosine 3'-monophosphate adducts were synthesized from reaction of HNE with 2'-deoxyguanosine 3'-monophosphate. After HPLC separation, these adduc...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970100r
更新日期:1997-11-01 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::Recent reports by Galeazzi and co-workers demonstrated the susceptibility of Abeta(1-42) to undergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formed dityrosine cross-links in Abeta(1-40) using these enzymatic conditions as well as a copper-H(2)O(2) method. The efficiency of dityrosi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx025666g
更新日期:2003-04-01 00:00:00
abstract::Prolonged exposure to estrogens correlates with an increased risk for breast cancer. One explanation is that estrogen metabolites cause mutations by reacting with DNA, leading to depurination. We describe an extraction procedure and a liquid chromatographic tandem mass spectrometric (LC/MS/MS) assay to detect estrone-...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8001737
更新日期:2008-08-01 00:00:00
abstract::Trans-Resveratrol (tRes) has been shown to have powerful antioxidant, anti-inflammatory, anticarcinogenic, and antiaging properties; however, its use as a therapeutic agent is limited by its rapid metabolism into its conjugated forms by UDP-glucuronosyltransferases (UGTs). The aim of the current study was to test the ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400408x
更新日期:2014-04-21 00:00:00
abstract::The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN, 1) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 2) are potent carcinogens in rodents. Bioactivation of NNN and NNK by cytochrome P450 enzymes generates a pyridyloxobutylating agent 6, which alkylates DNA to produce pyridyloxobutyl (POB)-DNA addu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx050351x
更新日期:2006-05-01 00:00:00
abstract::Chemical respiratory sensitization is an immunological process that manifests clinically mostly as occupational asthma and is responsible for 1 in 6 cases of adult asthma, although this may be an underestimate of the prevalence, as it is under-diagnosed. Occupational asthma results in unemployment for roughly one-thir...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00320
更新日期:2020-12-15 00:00:00
abstract::Quantitation of DNA adducts could provide critical information on the relationship between exposure to tobacco smoke and cancer risk in smokers. In this study, we developed a robust and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasin...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300282k
更新日期:2013-01-18 00:00:00