Application of capillary liquid chromatography coupled with tandem mass spectrometric methods to the rapid screening of adducts formed by the reaction of N-acetoxy-N-acetyl-2-aminofluorene with calf thymus DNA.

abstract：:Drug induced liver injury (DILI) can require significant risk management in drug development and on occasion can cause morbidity or mortality, leading to drug attrition. Optimizing candidates preclinically can minimize hepatotoxicity risk, but it is difficult to predict due to multiple etiologies encompassing DILI, of...

journal_title：Chemical research in toxicology

authors： Williams DP,Lazic SE,Foster AJ,Semenova E,Morgan P

更新日期：2020-01-21 00:00:00

abstract：:Environmental stress induces the synthesis of glucose-regulated proteins (Grps) in the endoplasmic reticulum (ER) and heat shock proteins (Hsps) in the cytoplasm. Iodoacetamide (IDAM), a prototypical alkyating agent, induces both Grp and Hsp synthesis in renal epithelial cells and causes necrosis which is prevented by...

journal_title：Chemical research in toxicology

authors： van De Water B,Wang Y,Asmellash S,Liu H,Zhan Y,Miller E,Stevens JL

更新日期：1999-10-01 00:00:00

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

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

更新日期：2006-04-01 00:00:00

abstract：:Jay Amin hydroxamic acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA's cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with ...

journal_title：Chemical research in toxicology

authors： Librizzi M,Caradonna F,Cruciata I,Dębski J,Sansook S,Dadlez M,Spencer J,Luparello C

更新日期：2017-12-18 00:00:00

abstract：:Hypoxia-inducible factor-1α (HIF-1α) is a critical regulator of cellular responses to hypoxia. Under normoxic conditions, the cellular HIF-1α level is regulated by hydroxylation by prolyl hydroxylases (PHDs), ubiquitylation, and proteasomal degradation. During hypoxia, degradation decreases, and its intracellular leve...

journal_title：Chemical research in toxicology

authors： Chowdhury R,Godoy LC,Thiantanawat A,Trudel LJ,Deen WM,Wogan GN

更新日期：2012-10-15 00:00:00

abstract：:Deoxyribose oxidation in DNA represents a biologically important facet of oxidative DNA damage that gives rise to protein-DNA cross-links and base adducts. Toward the goal of quantifying deoxyribose oxidation chemistry in cells, we report a method for the quantification of 3'-phosphoglycolaldehyde (PGA) residues, whic...

journal_title：Chemical research in toxicology

authors： Collins C,Awada MM,Zhou X,Dedon PC

更新日期：2003-12-01 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

authors： Alt C,Eyer P

更新日期：1998-10-01 00:00:00

abstract：:This paper reports on the analysis of the toxin content from Palythoa tuberculosa and Palythoa toxica samples collected off of the Hawaiian coast. Our work, based on in-depth high-resolution liquid chromatography-mass spectrometry analysis along with extensive NMR study, led us to structurally characterize 42-hydroxy-...

journal_title：Chemical research in toxicology

authors： Ciminiello P,Dell'aversano C,Dello Iacovo E,Fattorusso E,Forino M,Grauso L,Tartaglione L,Florio C,Lorenzon P,De Bortoli M,Tubaro A,Poli M,Bignami G

更新日期：2009-11-01 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：: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

authors： Dragovic S,Boerma JS,van Bergen L,Vermeulen NP,Commandeur JN

更新日期：2010-09-20 00:00:00

abstract：:Glutathione peroxidases and their mimics, e.g., ebselen or diaryl tellurides, efficiently reduce peroxynitrite/peroxynitrous acid (ONOO-/ONOOH) to nitrite and protect against oxidation and nitration reactions. Here, we report the second-order rate constant for the reaction of the reduced form of glutathione peroxidase...

journal_title：Chemical research in toxicology

authors： Briviba K,Kissner R,Koppenol WH,Sies H

更新日期：1998-12-01 00:00:00

abstract：:An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary hete...

journal_title：Chemical research in toxicology

authors： DeBruin LS,Martos PA,Josephy PD

更新日期：2001-11-01 00:00:00

abstract：:In the present study, values of the binding energy (BE) were calculated for the rat androgen receptor on a data set of 25 steroidal and nonsteroidal compounds for which published values of the observed binding affinity (K(i)) are available. A correlation between BE and pK(i) was evident (r(2) = 0.50) for the entire da...

journal_title：Chemical research in toxicology

authors： Ai N,DeLisle RK,Yu SJ,Welsh WJ

更新日期：2003-12-01 00:00:00

abstract：:There is limited and sometimes contradictory information about the genotoxicity of the polycyclic aromatic hydrocarbon benzo[ghi]perylene (B[ghi]P). Using recently developed metabolic toxicity screening arrays and a biocolloid reactor-LC-MS/MS approach, both featuring films of DNA and human metabolic enzymes, we demon...

journal_title：Chemical research in toxicology

authors： Pan S,Li D,Zhao L,Schenkman JB,Rusling JF

更新日期：2013-08-19 00:00:00

abstract：:A method for the analysis of N-acetylcysteine conjugates of catechol estrogens [catechol estrogen mercapturates (CE SRs)], which are likely to be urinary markers of estrogen-induced tumors, was established in this study. The characteristics of the method that was established were (1) cleanup of urine using the immunoa...

journal_title：Chemical research in toxicology

authors： Nakagomi M,Suzuki E

更新日期：2000-12-01 00:00:00

abstract：:The syntheses of potentially important metabolites of benzo[b]naphtho[2,1-d]thiophene ([2,1]BNT)--trans-1,2-dihydroxy-1,2-dihydrobenzo[b]naphtho[2,1- d]thiophene ([2,1]BNT-1,2-diol) and trans-3,4-dihydroxy-3,4-dihydrobenzo[b]naphtho[2,1-d]thiophene ([2,1]BNT-3,4-diol)--are described. The syntheses involved preparation...

journal_title：Chemical research in toxicology

authors： Misra B,Amin S

更新日期：1990-03-01 00:00:00

abstract：:A transient energy impairment with resultant release and subsequent reuptake of 5-hydroxytryptamine (5-HT) and NMDA receptor activation with consequent cytoplasmic superoxide (O(2)(-)(*)), nitric oxide (NO(*)), and peroxynitrite (ONOO(-)) generation have all been implicated in a neurotoxic cascade which ultimately lea...

journal_title：Chemical research in toxicology

authors： Jiang XR,Dryhurst G

更新日期：2002-10-01 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：:In this study, human glutathione transferases (GSTs) of alpha class have been assayed with the ultimate carcinogenic (-)-anti- and (+)-syn-diol epoxides (DEs) derived from the nonplanar dibenzo[a,l]pyrene (DBPDE) and the (+)-anti-diol epoxide of the planar benzo[a]pyrene [(+)-anti-BPDE] in the presence of glutathione ...

journal_title：Chemical research in toxicology

authors： Dreij K,Sundberg K,Johansson AS,Nordling E,Seidel A,Persson B,Mannervik B,Jernström B

更新日期：2002-06-01 00:00:00

abstract：:Toxicological studies assessing the safety of compounds for humans frequently use in vitro systems to characterize toxic responses in combination with transcriptomic analyses. Thus far, changes have mostly been investigated at the mRNA level. Recently, microRNAs have attracted attention because they are powerful negat...

journal_title：Chemical research in toxicology

authors： Lizarraga D,Gaj S,Brauers KJ,Timmermans L,Kleinjans JC,van Delft JH

更新日期：2012-04-16 00:00:00

abstract：:The reactions of calf thymus DNA with four 1,3-dialkyl-3-acyltriazenes were studied alone or in the presence of pig liver esterase in pH 7.4 phosphate buffer for varying lengths of time. The best alkylating agent in the absence of esterase was determined to be 1,3-dimethyl-3-carbethoxytriazene (DMC), followed in order...

journal_title：Chemical research in toxicology

authors： Kroeger-Koepke MB,Michejda CJ,Smith RH Jr

更新日期：1992-07-01 00:00:00

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

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

abstract：:The first method for generating (*)NO and O(2)(*)(-) at any known, constant ratio has been developed. Spermine NONOate and di(4-carboxybenzyl)hyponitrite decay with first-order kinetics and exactly equal rate constants (half-lives of 80 min) at 37 degrees C and pH 7.5 to give 200 and 40 mol % (*)NO and O(2)(*)(-), res...

journal_title：Chemical research in toxicology

authors： Hodges GR,Marwaha J,Paul T,Ingold KU

更新日期：2000-12-01 00:00:00

abstract：:The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and it has been hypothesized that this tissue contains cytochrome P450 enzymes (P450s) which catalyze the metabolic activation of these carcinogens. The metabolic capacity of the esophagus is not well characterized. In the study described he...

journal_title：Chemical research in toxicology

authors： von Weymarn LB,Murphy SE

更新日期：2001-10-01 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

authors： Stepanov I,Muzic J,Le CT,Sebero E,Villalta P,Ma B,Jensen J,Hatsukami D,Hecht SS

更新日期：2013-01-18 00:00:00

abstract：:Basic research, exploring the hypothesis that 2-(ω-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modificat...

journal_title：Chemical research in toxicology

authors： Salomon RG,Hong L,Hollyfield JG

更新日期：2011-11-21 00:00:00

abstract：:Coumadin (R/S-warfarin) anticoagulant therapy poses a risk to over 50 million Americans, in part due to interpersonal variation in drug metabolism. Consequently, it is important to understand how metabolic capacity is influenced among patients. Cytochrome P450s (P450 or CYP for a specific isoform) catalyze the first m...

journal_title：Chemical research in toxicology

authors： Jones DR,Kim SY,Guderyon M,Yun CH,Moran JH,Miller GP

更新日期：2010-05-17 00:00:00

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

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

abstract：:Acrolein (AC) and 4-hydroxy-2-nonenal (HNE) are endogenous bis-electrophiles that arise from the oxidation of polyunsaturated fatty acids. AC is also found in high concentrations in cigarette smoke and automobile exhaust. These reactive α,β-unsaturated aldehyde (enal) covalently modify nucleic acids, to form exocyclic...

journal_title：Chemical research in toxicology

authors： Kozekov ID,Turesky RJ,Alas GR,Harris CM,Harris TM,Rizzo CJ

更新日期：2010-11-15 00:00:00

abstract：:Estrogens and their oxidative metabolites, the catechol estrogens, have been implicated in the development of breast cancer; yet, relatively little is known about estrogen metabolism in the breast. To determine how the parent hormone, 17 beta-estradiol (E(2)), is metabolized, we used recombinant, purified phase I enzy...

journal_title：Chemical research in toxicology

authors： Dawling S,Hachey DL,Roodi N,Parl FF

更新日期：2004-09-01 00:00:00