abstract：:Antineoplastic therapy with anthracyclines like doxorubicin (DOX) and daunorubicin (DNR) is limited by the possible development of a dose-related cardiomyopathy. Secondary alcohol metabolites like doxorubicinol (DOXol) and daunorubicinol (DNRol), formed by cytoplasmic two-electron reductases, have been implicated as p...

journal_title：Chemical research in toxicology

authors： Silvestrini A,Meucci E,Vitali A,Giardina B,Mordente A

更新日期：2006-11-01 00:00:00

abstract：:We report on the generation of computer-based models for the prediction of the chromosome-damaging potential of chemicals as assessed in the in vitro chromosome aberration (CA) test. On the basis of publicly available CA-test results of more than 650 chemical substances, half of which are drug-like compounds, we gener...

journal_title：Chemical research in toxicology

authors： Rothfuss A,Steger-Hartmann T,Heinrich N,Wichard J

更新日期：2006-10-01 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

authors： Lancaster JR Jr

更新日期：2006-09-01 00:00:00

abstract：:Ochratoxin A (OTA) is a mycotoxin that shows potent nephrotoxicity and renal carcinogenicity in rodents. One hypothesis for OTA-induced tumor formation is based on its genotoxic properties that are promoted by oxidative metabolism. Like other chlorinated phenols, OTA undergoes an oxidative dechlorination process to ge...

journal_title：Chemical research in toxicology

authors： Tozlovanu M,Faucet-Marquis V,Pfohl-Leszkowicz A,Manderville RA

更新日期：2006-09-01 00:00:00

abstract：:The conformation of the crotonaldehyde-derived N(2)-[3-oxo-1(S)-methyl-propyl]-dG adduct in the oligodeoxynucleotide 5'-d(G(1)C(2)T(3)A(4)G(5)C(6)X(7)A(8)G(9)T(10)C(11)C(12))-3'.5'-d(G(13)G(14)A(15)C(16)T(17)C(18)G(19)C(20)T(21)A(22)G(23)C(2)(4))-3', where X = N(2)-[3-oxo-1(S)-methyl-propyl]-dG, is reported. This addu...

journal_title：Chemical research in toxicology

authors： Cho YJ,Wang H,Kozekov ID,Kozekova A,Kurtz AJ,Jacob J,Voehler M,Smith J,Harris TM,Rizzo CJ,Lloyd RS,Stone MP

更新日期：2006-08-01 00:00:00

abstract：:Formyl chloride has been indirectly implicated as an intermediate in the oxidation of CH(2)Cl(2) and proposed to be a product of the oxidation of some other compounds. Formyl chloride was synthesized and added to aqueous solutions, with CO formed as a product. The presence of glutathione (GSH) did not reduce the yield...

journal_title：Chemical research in toxicology

authors： Watanabe K,Guengerich FP

更新日期：2006-08-01 00:00:00

abstract：:It has previously been shown that malonaldehyde forms conjugates with acetaldehyde and that these conjugates react with nucleobases forming so-called conjugate adducts. In the current study, it is shown that conjugate adducts are also formed in calf thymus DNA when incubated simultaneously with malonaldehyde and aceta...

journal_title：Chemical research in toxicology

authors： Pluskota-Karwatka D,Pawłowicz AJ,Kronberg L

更新日期：2006-07-01 00:00:00

abstract：:The 2'-deoxyguanosine adduct of the dietary mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been synthesized and incorporated into DNA using solid state synthesis technology. The key step to obtaining the C8-dG adduct is a palladium (Xantphos-chelated)-catalyzed N-arylation (Buchwald-Hartwig reactio...

journal_title：Chemical research in toxicology

authors： Bonala R,Torres MC,Iden CR,Johnson F

更新日期：2006-06-01 00:00:00

abstract：:Five major products (adducts A(1a), A(1b), A(2), A(3,) and B) from the reaction of guanosine (Guo) with 4-oxo-2(E)-nonenal (ONE) were detected by liquid chromatography-mass spectrometry (LC-MS). Tandem MS (MS/MS) analysis of these compounds suggested that modifications to the nucleoside had been introduced. Adducts A(...

journal_title：Chemical research in toxicology

authors： Zhu P,Lee SH,Wehrli S,Blair IA

更新日期：2006-06-01 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

authors： Lao Y,Villalta PW,Sturla SJ,Wang M,Hecht SS

更新日期：2006-05-01 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：:The seaweed Fucus vesiculosus is unusual when compared with other algal species, in that it can survive in toxic-metal-contaminated aquatic environments. The metallothionein gene has been identified in F. vesiculosus by Kille and co-workers (Morris, C. A., Nicolaus, B., Sampson, V., Harwood, J. L., and Kille, P. (1999...

journal_title：Chemical research in toxicology

authors： Merrifield ME,Chaseley J,Kille P,Stillman MJ

更新日期：2006-03-01 00:00:00

abstract：:Thiacetazone (TAZ) and ethionamide (ETA) are, respectively, thiourea- and thioamide-containing second line antitubercular prodrugs for which there is an extensive clinical history of cross-resistance in Mycobacterium tuberculosis. EtaA, a recently identified flavin-containing monooxygenase (FMO), is responsible for th...

journal_title：Chemical research in toxicology

authors： Qian L,Ortiz de Montellano PR

更新日期：2006-03-01 00:00:00

abstract：:Benzo[a]pyrene diol epoxides (BPDEs) are the ultimate carcinogenic species of benzo[a]pyrene, a prototype polycyclic aromatic hydrocarbon (PAH). BPDE-modified DNA duplexes can adopt multiple conformations depending on the nature of the modified bases, the stereochemistry at the location of the covalent linkage, and th...

journal_title：Chemical research in toxicology

authors： Yang T,Huang Y,Cho BP

更新日期：2006-02-01 00:00:00

abstract：:2-Nitrosoamino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-NO-MeIQx) is a nitrosation product of the food carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and is proposed to form in vivo under inflammatory conditions. This study evaluated the stability and reactivity of N-NO-MeIQx to assess its possible r...

journal_title：Chemical research in toxicology

authors： Lakshmi VM,Hsu FF,Schut HA,Zenser TV

更新日期：2006-02-01 00:00:00

abstract：:Small particles of crystalline silicon dioxide (crystallites) are exceptionally toxic. Inhalation of quartz crystallites causes silicosis, a devastating lung disease afflicting miners, particularly coal and stone workers. Poly(vinylpyridine-N-oxide)s (PVPNOs) have been applied in the prevention and treatment of silico...

journal_title：Chemical research in toxicology

authors： Goldstein S,Czapski G,Heller A

更新日期：2006-01-01 00:00:00

abstract：:Strong evidence supports the idea that specific metabolites of estrogens, mainly catechol estrogen-3,4-quinones, can react with DNA to become endogenous initiators of breast, prostate, and other human cancers. Oxidation of the catechol estrogen metabolites 4-hydroxyestradiol (4-OHE2) and 2-OHE2 leads to the quinones, ...

journal_title：Chemical research in toxicology

authors： Zahid M,Kohli E,Saeed M,Rogan E,Cavalieri E

更新日期：2006-01-01 00:00:00

abstract：:Previously, we reported a new animal model of an idiosyncratic drug reaction in which nevirapine causes a skin rash in some rats that has characteristics similar to the reaction that occurs in humans. Strong evidence that the reaction is immune-mediated was found; specifically, low-dose pretreatment induced tolerance,...

journal_title：Chemical research in toxicology

authors： Shenton JM,Popovic M,Chen J,Masson MJ,Uetrecht JP

更新日期：2005-12-01 00:00:00

abstract：:Hydroxyl radical can be induced from Fenton reaction or gamma radiolysis of water. It can add preferentially to the C5 position of thymidine to give the 5-hydroxy-5,6-dihydrothymidin-6-yl radical. In this report, we examined the independent generation and reactivity of this radical in oligodeoxyribonucleotides (ODNs)....

journal_title：Chemical research in toxicology

authors： Zhang Q,Wang Y

更新日期：2005-12-01 00:00:00

abstract：:Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydra...

journal_title：Chemical research in toxicology

authors： Kaminskas LM,Pyke SM,Burcham PC

更新日期：2005-11-01 00:00:00

abstract：:Cholyl adenylate is a putative intermediate for biosynthesis of cholic acid-coenzyme A (CoA) thioester conjugates by acyl-CoA synthetase. Early studies showed the conjugated acid anhydride moiety of cholyl adenylate to be reactive, attacking proteins to form protein-cholic acid adducts. In the present study, to clarif...

journal_title：Chemical research in toxicology

authors： Takamura-Enya T,Mano N,Kawahara N,Goto J,Wakabayashi K

更新日期：2005-11-01 00:00:00

abstract：:DNA conformational change and breakage induced by Cr(VI)-GSH interaction were characterized by the integrated tools of electrochemistry, atomic force microscopy (AFM), and DNA electrophoresis. While electrochemistry confirmed the formation of the active species generated from Cr(VI)-GSH reduction, which causes the DNA...

journal_title：Chemical research in toxicology

authors： Yang PH,Gao HY,Cai J,Chiu JF,Sun H,He QY

更新日期：2005-10-01 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

authors： Gardner I,Popović M,Zahid N,Uetrecht JP

更新日期：2005-09-01 00:00:00

abstract：:The procarcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed during the cooking of foods. Metabolism of PhIP by CYP1A2 differs substantially between humans and rodents, with more N2-hydroxylation (activation) and less 4'-hydroxylation (detoxication) in humans....

journal_title：Chemical research in toxicology

authors： Cheung C,Ma X,Krausz KW,Kimura S,Feigenbaum L,Dalton TP,Nebert DW,Idle JR,Gonzalez FJ

更新日期：2005-09-01 00:00:00

abstract：:To reveal the roles of Y family DNA polymerases in the mutagenesis induced by oxidatively damaged DNA precursors, 2-hydroxy-dATP (2-OH-dATP) and 8-hydroxy-dGTP (8-OH-dGTP) were introduced into Escherichia coli strains deficient in the Y family polymerases, DNA polymerase IV (pol IV, encoded by the dinB gene) and DNA p...

journal_title：Chemical research in toxicology

authors： Satou K,Yamada M,Nohmi T,Harashima H,Kamiya H

更新日期：2005-08-01 00:00:00

abstract：:The two major metabolites after S-oxygenation of dimethylthiourea (dimethylaminoiminomethane sulfinic acid, DMAIMSA, and dimethylaminoiminomethane sulfonic acid, DMAIMSOA) were synthesized and tested for their reactivities in the presence of mild oxidants, aqueous iodine and acidic iodate. The stoichiometry of the iod...

journal_title：Chemical research in toxicology

authors： Otoikhian A,Simoyi RH,Petersen JL

更新日期：2005-07-01 00:00:00

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

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

更新日期：2005-06-01 00:00:00

abstract：:Exposure to the tobacco-related nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine is carcinogenic to humans. Metabolic activation of NNK leads to the formation of DNA adducts, which play a critical role in NNK carcinogenesis. Adducts specific to NNK result from covalent linkag...

journal_title：Chemical research in toxicology

authors： Sturla SJ,Scott J,Lao Y,Hecht SS,Villalta PW

更新日期：2005-06-01 00:00:00

abstract：:The metabolic pathway of tetrodotoxin (TTX), a powerful and specific voltage-gated sodium channel blocker, has not been well-clarified either in TTX-poisoned patients or in puffer fish. 4-S-CysteinylTTX (4-CysTTX) was isolated from the liver of the puffer fish, Fugu pardalis, as the first adduct of TTX with thiol. The...

journal_title：Chemical research in toxicology

authors： Yotsu-Yamashita M,Goto A,Nakagawa T

更新日期：2005-05-01 00:00:00

abstract：:Carcinogenic polycyclic aromatic hydrocarbons (PAH), e.g., benzo[a]pyrene (BaP), possess a bay region comprising an ortho-fused benzene ring. Benzo[ghi]perylene (BghiP) represents the group of PAHs lacking such a "classic" bay region and hence cannot be metabolically converted like BaP to bay region dihydrodiol epoxid...

journal_title：Chemical research in toxicology

authors： Platt KL,Grupe S

更新日期：2005-04-01 00:00:00

abstract：:The reactions of aqueous ClO2 with tyrosine, N-acetyltyrosine, and dopa (3,4-dihydroxyphenylalanine) are investigated from pH 4 to 7. The reaction rates increase greatly with pH to give a series of oxidized products. Tyrosine and N-acetyltyrosine have similar reactivities with second-order rate constants (25.0 degrees...

journal_title：Chemical research in toxicology

authors： Napolitano MJ,Green BJ,Nicoson JS,Margerum DW

更新日期：2005-03-01 00:00:00

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

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

更新日期：2005-02-01 00:00:00

abstract：:The purpose of this study was to investigate the degree of chlorination of catechol (CAT) derivatives of pentachlorophenol (PCP) on the induction of cytotoxicity and DNA damaging effects in calf thymus DNA (ct-DNA) and in two human breast carcinoma cell lines. Results indicated that with the addition of the transition...

journal_title：Chemical research in toxicology

authors： Lin CH,Leow HT,Huang SC,Nakamura J,Swenberg JA,Lin PH

更新日期：2005-02-01 00:00:00

abstract：:Toxicity data for 82 aliphatic chemicals with an alpha,beta-unsaturated substructure were compiled. Toxicity was assessed in the 2-day Tetrahymena pyriformis population growth impairment assay. Toxic potency [log(IGC50(-1))] for most of these chemicals was in excess of baseline narcosis as quantified by the 1-octanol/...

journal_title：Chemical research in toxicology

authors： Schultz TW,Netzeva TI,Roberts DW,Cronin MT

更新日期：2005-02-01 00:00:00

abstract：:N'-Nitrosonornicotine (NNN) and N-nitrosopiperidine (NPIP) are potent esophageal and nasal cavity carcinogens in rats and pulmonary carcinogens in mice. N-Nitrosopyrrolidine (NPYR) induces mainly liver tumors in rats and is a weak pulmonary carcinogen in mice. These nitrosamines may be causative agents in human cancer...

journal_title：Chemical research in toxicology

authors： Wong HL,Murphy SE,Hecht SS

更新日期：2005-01-01 00:00:00

abstract：:NADPH in microsomes reduces the hydroxocob(III)alamin form of vitamin B12 to cob(II)alamin and the supernucleophilic cob(I)alamin, which are both highly reactive toward xenobiotic epoxides formed by mammalian metabolism of dienes such as the industrially important chemicals chloroprene and 1,3-butadiene. With styrene,...

journal_title：Chemical research in toxicology

authors： Watson WP,Munter T,Golding BT

更新日期：2004-12-01 00:00:00

abstract：:1,2,3,4-Diepoxybutane (DEB) is a prominent carcinogenic metabolite of 1,3-butadiene (1,3-BD), an important industrial chemical and an environmental pollutant found in cigarette smoke and automobile exhaust. DEB is capable of inducing a variety of genotoxic effects, including point mutations, large deletions, and chrom...

journal_title：Chemical research in toxicology

authors： Park S,Hodge J,Anderson C,Tretyakova N

更新日期：2004-12-01 00:00:00

abstract：:Oxidative stress is believed to play a role in the pathogenesis of several diseases, including diabetes and inborn errors of metabolism. The types of oxidative damage observed in these pathologies have been attributed to the excessive production of reactive intermediates relating to the accumulation of toxic metabolit...

journal_title：Chemical research in toxicology

authors： Royer LO,Knudsen FS,de Oliveira MA,Tavares MF,Bechara EJ

更新日期：2004-12-01 00:00:00

abstract：:Two novel pectenotoxins (PTXs) were detected by LC-MS in solid phase extracts of net hauls taken at Flødevigen, Norway, in June 2002 that were dominated by Dinophysis acuminata and Dinophysis norvegica. The new compounds were isolated as minor components from a large collection of a Dinophysis acuta-dominated bloom ob...

journal_title：Chemical research in toxicology

authors： Miles CO,Wilkins AL,Samdal IA,Sandvik M,Petersen D,Quilliam MA,Naustvoll LJ,Rundberget T,Torgersen T,Hovgaard P,Jensen DJ,Cooney JM

更新日期：2004-11-01 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

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

更新日期：2004-11-01 00:00:00