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

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

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

authors： Obach RS,Kalgutkar AS,Ryder TF,Walker GS

更新日期：2008-09-01 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

authors： Zhang Q,Aft RL,Gross ML

更新日期：2008-08-01 00:00:00

abstract：:The present study describes a novel integrated approach for rapid analysis of reactive metabolites with a linear ion trap mass spectrometer (LTQ). In this approach, an isotope pattern-dependent scanning method was applied to the data acquisition of glutathione (GSH)-trapped reactive metabolites. Recorded full-scan MS ...

journal_title：Chemical research in toxicology

authors： Ma L,Wen B,Ruan Q,Zhu M

更新日期：2008-07-01 00:00:00

abstract：:( E)-4-Hydroxynon-2-enal (HNE), an electrophilic bifunctional cytotoxic lipid peroxidation product, forms covalent adducts with nucleophilic side chains of amino acid residues. HNE-derived adducts have been implicated in many pathophysiological processes including atherosclerosis, diabetes, and Alzheimer's disease. Tr...

journal_title：Chemical research in toxicology

authors： Annangudi SP,Deng Y,Gu X,Zhang W,Crabb JW,Salomon RG

更新日期：2008-07-01 00:00:00

abstract：:Estrogen exposure through early menarche, late menopause, and hormone replacement therapy increases the risk factor for hormone-dependent cancers. Although the molecular mechanisms are not completely established, DNA damage by quinone electrophilic reactive intermediates, derived from estrogen oxidative metabolism, is...

journal_title：Chemical research in toxicology

authors： Chandrasena RE,Edirisinghe PD,Bolton JL,Thatcher GR

更新日期：2008-07-01 00:00:00

abstract：:Naphtho[8,1,2- ghi]chrysene, commonly known as naphtho[1,2- e]pyrene (N[1,2- e]P) is a widespread environmental pollutant, identified in coal tar extract, air borne particulate matter, marine sediment, cigarette smoke condensate, and vehicle exhaust. Herein, we determined the ability of rat liver microsomes to metabol...

journal_title：Chemical research in toxicology

authors： Sharma AK,Gowdahalli K,Gimbor M,Amin S

更新日期：2008-05-01 00:00:00

abstract：:PAHs (polycyclic aromatic hydrocarbons) are suspect lung cancer carcinogens that must be metabolically converted into DNA-reactive metabolites. P4501A1/P4501B1 plus epoxide hydrolase activate PAH to (+/-)- anti-benzo[ a]pyrene diol epoxide ((+/-)- anti-BPDE), which causes bulky DNA adducts. Alternatively, aldo-keto re...

journal_title：Chemical research in toxicology

authors： Park JH,Gelhaus S,Vedantam S,Oliva AL,Batra A,Blair IA,Troxel AB,Field J,Penning TM

更新日期：2008-05-01 00:00:00

abstract：:The increasing use of fullerene nanomaterials has prompted widespread concern over their biological effects. Herein, we have studied the phototoxicity of gamma-cyclodextrin bicapped pristine C 60 [(gamma-CyD) 2/C 60] and its water-soluble derivative C 60(OH) 24 toward human keratinocytes. Our results demonstrated that...

journal_title：Chemical research in toxicology

authors： Zhao B,He YY,Bilski PJ,Chignell CF

更新日期：2008-05-01 00:00:00

abstract：:The use of powerful analytical technologies to detect endogenous carbonyls formed as byproducts of oxidative cell injury has revealed that these species contribute to many human diseases. As electrophiles, they are attacked by reactive centers in cell macromolecules to form adducts, the levels of which serve as useful...

journal_title：Chemical research in toxicology

authors： Burcham PC

更新日期：2008-04-01 00:00:00

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

authors： Bandele OJ,Osheroff N

更新日期：2008-04-01 00:00:00

abstract：:Witch hazel ( Hammamelis virginiana) bark is a rich source of both condensed and hydrolizable oligomeric tannins. From a polyphenolic extract soluble in both ethyl acetate and water, we have generated fractions rich in pyrogallol-containing polyphenols (proanthocyanidins, gallotannins, and gallates). The mixtures were...

journal_title：Chemical research in toxicology

authors： Touriño S,Lizárraga D,Carreras A,Lorenzo S,Ugartondo V,Mitjans M,Vinardell MP,Juliá L,Cascante M,Torres JL

更新日期：2008-03-01 00:00:00

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 ...

journal_title：Chemical research in toxicology

authors： Kellert M,Wagner S,Lutz U,Lutz WK

更新日期：2008-03-01 00:00:00

abstract：:The regulation of cellular stress responses to electrophiles and oxidants is mediated by the transcription factor NF-E2-related factor 2 (Nrf2), which, in turn, is regulated by CUL-E3 (CUL3) ligase-mediated ubiquitylation. The Kelch-like ECH-associated protein 1 (Keap1) serves as an adapter between CUL3 and Nrf2. We u...

journal_title：Chemical research in toxicology

authors： Rachakonda G,Xiong Y,Sekhar KR,Stamer SL,Liebler DC,Freeman ML

更新日期：2008-03-01 00:00:00

abstract：:We propose here a combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) metabolic profiling strategy to elucidate the toxicity in rats induced by orally administered multiglycosides of Tripterygium wilfordii Hook. f. (GTW) in multiple organs including the kidney, liv...

journal_title：Chemical research in toxicology

authors： Chen M,Ni Y,Duan H,Qiu Y,Guo C,Jiao Y,Shi H,Su M,Jia W

更新日期：2008-02-01 00:00:00

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

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

更新日期：2008-02-01 00:00:00

abstract：:Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and the aryl hydrocarbon receptor (AhR) work as environmental sensors in human tissues. These proteins are members of the helix-loop-helix/Per-ARNT-SIM transcription factor family and form heterodimers with the aryl hydrocarbon receptor nuclear translocator. HIF-1 alpha c...

journal_title：Chemical research in toxicology

authors： Seifert A,Katschinski DM,Tonack S,Fischer B,Navarrete Santos A

更新日期：2008-02-01 00:00:00

abstract：:The P450 type cytochromes are responsible for the metabolism of a wide variety of xenobiotics and endogenous compounds. Although P450-catalyzed reactions are generally thought to lead to detoxication of xenobiotics, the reactions can also produce reactive intermediates that can react with cellular macromolecules leadi...

journal_title：Chemical research in toxicology

authors： Hollenberg PF,Kent UM,Bumpus NN

更新日期：2008-01-01 00:00:00

abstract：:Contact allergy is caused by a wide range of chemicals after skin contact. Its clinical manifestation, allergic contact dermatitis (ACD), is developed upon repeated contact with the allergen. This perspective focuses on two areas that have yielded new useful information during the last 20 years: (i) structure-activity...

journal_title：Chemical research in toxicology

authors： Karlberg AT,Bergström MA,Börje A,Luthman K,Nilsson JL

更新日期：2008-01-01 00:00:00

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

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

abstract：:Previous studies have demonstrated that reactive dicarbonyl compounds [e.g., methylglyoxal (MGO) and glyoxal (GO)] irreversibly and progressively modify proteins over time and yield advanced glycation end products (AGEs), which are thought to contribute to the development of diabetes mellitus and its subsequent compli...

journal_title：Chemical research in toxicology

authors： Sang S,Shao X,Bai N,Lo CY,Yang CS,Ho CT

更新日期：2007-12-01 00:00:00

abstract：:The two diastereomeric forms (5'S) and (5'R) of 5',8-cyclo-2'-deoxyguanosine have been synthesized and fully characterized. They have been used as references for the investigation of gamma-irradiation of 2'-deoxyguanosine and photolysis of 8-bromo-2'-deoxyguanosine in aqueous solutions. The observed (5'R)/(5'S) ratio ...

journal_title：Chemical research in toxicology

authors： Chatgilialoglu C,Bazzanini R,Jimenez LB,Miranda MA

更新日期：2007-12-01 00:00:00

abstract：:The current study examined the bioactivation potential of a nonpeptidyl thrombopoietin receptor agonist, 1-(3-chloro-5-((4-(4-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-yl)carbamoyl)pyridine-2-yl)piperidine-4-carboxylic acid (1), containing a 2-carboxamido-4-arylthiazole moiety in the core structure. Toxicological ris...

journal_title：Chemical research in toxicology

authors： Kalgutkar AS,Driscoll J,Zhao SX,Walker GS,Shepard RM,Soglia JR,Atherton J,Yu L,Mutlib AE,Munchhof MJ,Reiter LA,Jones CS,Doty JL,Trevena KA,Shaffer CL,Ripp SL

更新日期：2007-12-01 00:00:00

abstract：:Interstrand cross-links are minor components of the collection of products formed in DNA by ionizing radiation. Through their formation by other damaging agents, it is known that interstrand cross-links exert significant effects on replication and transcription. The structures of DNA interstrand cross-links produced a...

journal_title：Chemical research in toxicology

authors： Ding H,Greenberg MM

更新日期：2007-11-01 00:00:00

abstract：:Previously, we identified two distinct metabonomic phenotypes in Sprague-Dawley rats sourced from two different rooms (colonies) in the Charles River, Raleigh facility [Robosky, L. C., Wells, D. F., Egnash, L. A., Manning, M. L., Reily, M. D., and Robertson, D. G. (2005) Metabonomic identification of two distinct phen...

journal_title：Chemical research in toxicology

authors： Rohde CM,Wells DF,Robosky LC,Manning ML,Clifford CB,Reily MD,Robertson DG

更新日期：2007-10-01 00:00:00

abstract：:By the action of UVA light, fluphenazine reacted with nucleophiles through a mechanism involving defluorination of its trifluoromethyl group, giving rise to carboxylic acid derivatives that were easily detected by electrospray mass spectrometry. This photoreaction took place with alcohols, sulphydryls, and amines. Whe...

journal_title：Chemical research in toxicology

authors： Caffieri S,Miolo G,Seraglia R,Dalzoppo D,Toma FM,van Henegouwen GM

更新日期：2007-10-01 00:00:00

abstract：:The kinetics and mechanisms of the hydrolysis of cysteine thiosulfinate ester (CyS(O)SCy ( x- ), x = 0-2) have been investigated by stopped-flow spectrophotometry between pH 6 and pH 14. The rate-limiting reaction of hydroxide is observed for pH < 13. More complicated kinetics are observed above pH 13, where the hydro...

journal_title：Chemical research in toxicology

authors： Nagy P,Ashby MT

更新日期：2007-09-01 00:00:00

abstract：:A diverse series of polarized alpha,beta-unsaturated and related compounds were evaluated for reactivity with a spectrophotometric assay using the sulfhydryl group in the form of the cysteine residue of the tripeptide GSH as a model nucleophile. The reactive end point (RC 50) calculations were compared to previously d...

journal_title：Chemical research in toxicology

authors： Schultz TW,Yarbrough JW,Hunter RS,Aptula AO

更新日期：2007-09-01 00:00:00

abstract：:The primary products of one-electron oxidation of clozapine and olanzapine, very effective atypical antipsychotic drugs, have been spectroscopically characterized. The oxidation process has been studied under glassy matrix conditions and by a pulse radiolysis technique in aqueous solution. The rate constants for the o...

journal_title：Chemical research in toxicology

authors： Sikora A,Adamus J,Marcinek A

更新日期：2007-08-01 00:00:00

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

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

更新日期：2007-05-01 00:00:00

abstract：:Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and non-combatants is potentially frequent and widespread. DU is considered a suspected human carcinogen, affecting the bronchial cells of the lung. However, few investigations have studied DU in human bronchial cell...

journal_title：Chemical research in toxicology

authors： Wise SS,Thompson WD,Aboueissa AM,Mason MD,Wise JP Sr

更新日期：2007-05-01 00:00:00

abstract：:Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted appreciable focus to their application in cancer chemotherapy. Redox-inactive Fe chelator complexe...

journal_title：Chemical research in toxicology

authors： Kalinowski DS,Richardson DR

更新日期：2007-05-01 00:00:00

abstract：:N-Nitrosopyrrolidine (NPYR) is a well-established hepatocarcinogen in the rat. NPYR requires metabolic activation by cytochrome P450-catalyzed alpha-hydroxylation to express its carcinogenic activity. This produces alpha-hydroxyNPYR (2), which spontaneously ring opens to 4-oxobutanediazohydroxide (4), a highly reactiv...

journal_title：Chemical research in toxicology

authors： Wang M,Lao Y,Cheng G,Shi Y,Villalta PW,Hecht SS

更新日期：2007-04-01 00:00:00

abstract：:A diverse series of aliphatic alpha,beta-unsaturated esters, ketones, and aldehydes were evaluated for reactivity with the model nucleophile sulfhydryl group in the form of the cysteine residue of the tripeptide glutathione; the reactive end point (RC50) was then related to aquatic toxicity (IGC50) assessed in the Tet...

journal_title：Chemical research in toxicology

authors： Yarbrough JW,Schultz TW

更新日期：2007-03-01 00:00:00

abstract：:DNA-DNA cross-linking by 1,2,3,4-diepoxybutane (DEB) is considered the molecular basis for its potent cytotoxic and genotoxic effects. DEB reactions with DNA initially lead to N7-(2'-hydroxy-3',4'-epoxybut-1'-yl)-guanine monoadducts, which can then alkylate neighboring DNA bases to form bifunctional lesions. We recent...

journal_title：Chemical research in toxicology

authors： Tretyakova N,Livshits A,Park S,Bisht B,Goggin M

更新日期：2007-02-01 00:00:00

abstract：:On the basis of a large number of reports concerning the detection of lipid peroxidation products as biomarkers in human diseases, there is no doubt that their steady-state levels increase under pathophysiological states associated with oxidative stress. The key question is whether they play any causative roles. This ...

journal_title：Chemical research in toxicology

authors： Uchida K

更新日期：2007-01-01 00:00:00

abstract：:A new procedure has been developed for the extraction of 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and other heterocyclic aromatic amines from human breast milk samples. Extracts were analyzed by high-performance liquid chromatography/electrospray ionization/tandem mass spectrometry (HPLC/ESI-MS/MS) with...

journal_title：Chemical research in toxicology

authors： Scott KA,Turesky RJ,Wainman BC,Josephy PD

更新日期：2007-01-01 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

authors： Smith DA,Obach RS

更新日期：2006-12-01 00:00:00

abstract：:Previous work has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes porphyria, enhanced by iron, in C57BL/6J mice with marked accumulation in the liver of uroporphyrin I and III isomers and heptacarboxylic acid III and is one model of human porphyria cutanea tarda. Preliminary examination by HPLC also indic...

journal_title：Chemical research in toxicology

authors： Lim CK,Danton M,Clothier B,Smith AG

更新日期：2006-12-01 00:00:00

abstract：:Retinyl palmitate (RP) is frequently used as an ingredient in cosmetics and other retail products. We previously reported that, under UVA light irradiation, RP is facilely decomposed into multiple products, including anhydroretinol (AR) and 5,6-epoxyretinyl palmitate (5,6-epoxy-RP). We also determined that combined tr...

journal_title：Chemical research in toxicology

authors： Mei N,Xia Q,Chen L,Moore MM,Chen T,Fu PP

更新日期：2006-11-01 00:00:00