Reevaluation of the effect of ellagic acid on N-methyl-N-nitrosourea DNA alkylation and mutagenicity.


:N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N7, guanine O6, and adenine N3. Dixit and Gold [(1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8039-8043] reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU in Salmonella typhimurium strain TA 100, inhibited salmon sperm DNA alkylation by [3H]MNU, and also greatly reduced the ratio of guanine O6 to guanine N7 alkylation. We have examined the MNU-induced alkylation of calf thymus DNA and evaluated the effect of ellagic acid on this binding. Ellagic acid had only a slight effect on total alkylation and did not alter the ratio of methylation at guanine-O6 and -N7 positions. In further experiments, ellagic acid did not significantly inhibit MNU mutagenicity. These findings do not support the potential use of ellagic acid as an inhibitor of biological damage induced by nitrosoureas.


Chem Res Toxicol


Lord HL,Josephy PD,Snieckus VA




Has Abstract


1990-05-01 00:00:00












  • Oxidative conversion by rat liver microsomes of 2-naphthyl isothiocyanate to 2-naphthyl isocyanate, a genotoxicant.

    abstract::The present study investigated the oxidative metabolism of 2-naphthyl isothiocyanate catalyzed by rat liver microsomes. Incubation of 2-naphthyl isothiocyanate, microsomes, and NADPH yielded either N,N'-di-2-naphthylurea or, on inclusion of 2-aminofluorene in the incubations, N-2-naphthyl-N'-2-fluorenylurea. These ure...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lee MS

    更新日期:1992-11-01 00:00:00

  • In vivo cadmium mobilization by three novel bis(carbodithioates).

    abstract::Four novel cadmium-chelating agents N,N'di(D-glucosyl)alkanediamine-N,N'-bis(carbodithioates) 4a-e were prepared as disodium salts of the general formula (CH2)n[N(CS2Na)CH2(CHOH)4CH2OH]2, where n = 7, 8, 10, and 12. They were synthesized by the reductive coupling of 2 mol of alpha-D-(+)-glucose (1) with 1 mol of the c...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Singh PK,Jones MM,Kostial K,Blanusa M,Piasek M

    更新日期:1996-01-01 00:00:00

  • Exposure to the Heavy-Metal Lead Induces DNA Copy Number Alterations in Zebrafish Cells.

    abstract::DNA copy number variants are associated with the development of complex neurological diseases and disorders including autism spectrum disorder, schizophrenia, Alzheimer's disease, and Parkinson's disease. Exposure to multiple environmental chemicals including various heavy metals is suggested as a risk factor in these...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lee J,Freeman JL

    更新日期:2020-08-17 00:00:00

  • Environmental fine particulate matter (PM 2.5) activates the RAW 264.7 macrophage cell line even at very low concentrations as revealed by 1H NMR.

    abstract::Because of the association between inhalation of airborne particulate matter (PM) and human respiratory and cardiovascular disease, it is necessary to understand the tissue damage induced by these particles. One of the cell types principally involved in the body's reaction to PM are macrophages, which remove particles...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Santini MT,Rainaldi G,Ferrante A,Romano R,Clemente S,Motta A,De Berardis B,Balduzzi M,Paoletti L,Indovina PL

    更新日期:2004-01-01 00:00:00

  • Synthesis, Characterization, and Identification of New in Vitro Covalent DNA Adducts of Divinyl Sulfone, an Oxidative Metabolite of Sulfur Mustard.

    abstract::Divinyl sulfone (DVS) is an important oxidative metabolic product of sulfur mustard (SM) in vitro and in vivo. Although DVS is not a classical blister agent, its high reactivity and toxicity induced by vinyl groups can also cause blisters like SM upon contact with the skin, eyes, and respiratory organs. The purpose of...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Lv S,Zhang Y,Xu B,Xu H,Zhao Y,Chen J,Gao Z,Wu J,Xie J

    更新日期:2017-10-16 00:00:00

  • Problematic detoxification of estrogen quinones by NAD(P)H-dependent quinone oxidoreductase and glutathione-S-transferase.

    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

    pub_type: 杂志文章


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

    更新日期:2008-07-01 00:00:00

  • Microsomal biotransformation of benzo[ghi]perylene, a mutagenic polycyclic aromatic hydrocarbon without a "classic" bay region.

    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

    pub_type: 杂志文章


    authors: Platt KL,Grupe S

    更新日期:2005-04-01 00:00:00

  • Computational models for predicting the binding affinities of ligands for the wild-type androgen receptor and a mutated variant associated with human prostate cancer.

    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

    pub_type: 杂志文章


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

    更新日期:2003-12-01 00:00:00

  • DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure.

    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


    authors: Gao L,Mutlu E,Collins LB,Walker NJ,Hartwell HJ,Olson JR,Sun W,Gold A,Ball LM,Swenberg JA

    更新日期:2017-03-20 00:00:00

  • Enhancement of 2'-deoxyguanosine hydroxylation and DNA damage by coal and oil fly ash in relation to particulate metal content and availability.

    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


    authors: Prahalad AK,Inmon J,Ghio AJ,Gallagher JE

    更新日期:2000-10-01 00:00:00

  • Pivotal role for two electron reduction in 2,3-dimethoxy-1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone metabolism and kinetics in vivo that prevents liver redox stress.

    abstract::2,3-dimethoxy-1,4-naphthoquinone (CAS-RN 6959-96-3) (DMNQ) and 2-methyl-1,4-naphthoquinone (CAS-RN 58-27-5) (MNQ:menadione) are effective one electron redox cycling chemicals in vitro. In addition, in vitro MNQ forms a thioether conjugate with glutathione by nucleophilic attack at the third carbon. In contrast, here w...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Parry JD,Pointon AV,Lutz U,Teichert F,Charlwood JK,Chan PH,Athersuch TJ,Taylor EL,Singh R,Luo J,Phillips KM,Vetillard A,Lyon JJ,Keun HC,Lutz WK,Gant TW

    更新日期:2009-04-01 00:00:00

  • Future of toxicology--lipid peroxidation in the future: from biomarker to etiology.

    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

    pub_type: 杂志文章


    authors: Uchida K

    更新日期:2007-01-01 00:00:00

  • Molecular recognition between oligopeptides and nucleic acids: DNA binding selectivity of a series of 1,2,4-triazole-containing lexitropsins.

    abstract::The synthesis of a series of 1,2,4-triazole-containing oligopeptide lexitropsins related to the natural antitumor antibiotic distamycin is described. The binding properties of these new agents to both native DNAs and synthetic polydeoxyribonucleotides were determined by UV absorption and circular dichroism studies. Th...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Rao KE,Krowicki K,Burckhardt G,Zimmer C,Lown JW

    更新日期:1991-03-01 00:00:00

  • Urinary sulfur-containing metabolite produced by intestinal bacteria following oral administration of dimethylarsinic acid to rats.

    abstract::Our long-term oral administration of dimethylarsinic acid (DMAV) in rats revealed that three unidentified metabolites, M-1, M-2, and M-3, were detected in urine and feces. DMAV and trimethylarsine oxide (TMAO) were converted to M-2 and M-3 and M-1 by Escherichia coli strain A3-6 isolated from the ceca of DMAV-administ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Yoshida K,Kuroda K,Zhou X,Inoue Y,Date Y,Wanibuchi H,Fukushima S,Endo G

    更新日期:2003-09-01 00:00:00

  • Role of human glutathione S-transferases in the inactivation of reactive metabolites of clozapine.

    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


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

    更新日期:2010-09-20 00:00:00

  • Mutagenesis induced by oxidized DNA precursors: roles of Y family DNA polymerases in Escherichia coli.

    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

    pub_type: 杂志文章


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

    更新日期:2005-08-01 00:00:00

  • Structure of an Unusual Tetracyclic Deoxyguanosine Adduct: Implications for Frameshift Mutagenicity of ortho-Cyano Nitroanilines.

    abstract::Nitroaromatic compounds represent a major class of industrial chemicals that are also found in nature. Polycyclic derivatives are regarded as potent mutagens and carcinogens following bioactivation to produce nitrenium electrophiles that covalently modify DNA to afford N-linked C8-2'-deoxyguanosine (C8-dG) lesions tha...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Manning TW,Al-Abdul-Wahid MS,Manderville RA,Josephy PD,Kung RW,Wetmore SD

    更新日期:2020-02-17 00:00:00

  • Chemoavailability of Organic Electrophiles: Impact of Hydrophobicity and Reactivity on Their Aquatic Excess Toxicity.

    abstract::Organic electrophiles have been recognized as important components of the exposome that can be characterized as cumulative totality of exposure in the organism in response to environmental perturbation. For such compounds, chemical reactivity may contribute significantly to the toxicological profile through covalent a...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Böhme A,Laqua A,Schüürmann G

    更新日期:2016-06-20 00:00:00

  • Metabolic studies on phencyclidine: characterization of a phencyclidine iminium ion metabolite.

    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


    authors: Hoag MK,Schmidt-Peetz M,Lampen P,Trevor A,Castagnoli N Jr

    更新日期:1988-03-01 00:00:00

  • Synthesis and characterization of estrogen 2,3- and 3,4-quinones. Comparison of DNA adducts formed by the quinones versus horseradish peroxidase-activated catechol estrogens.

    abstract::Catechol estrogens (CE) are among the major metabolites of estrone (E1) and 17 beta-estradiol (E2). Oxidation of these metabolites to semiquinones and quinones could generate ultimate carcinogenic forms of E1 and E2. The 2,3- and 3,4-quinones of E1 and E2 were synthesized by MnO2 oxidation of the corresponding CE, fol...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Dwivedy I,Devanesan P,Cremonesi P,Rogan E,Cavalieri E

    更新日期:1992-11-01 00:00:00

  • Reaction of CO2 with ONOO-: One Molecule of CO2 Is Not Enough.

    abstract::With CO2 present in excess, ONOO- reacts to form an adduct in solution and in the solid state, most likely ONOOCO2-. In solution, the adduct appears within 2 ms and absorbs at 300 with an extinction coefficient, which is either 50% or 100% (preferred) of that of ONOO-, 1.70 × 103 M-1 cm-1, and at 685 nm with an extinc...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Serrano-Luginbuehl S,Kissner R,Koppenol WH

    更新日期:2018-08-20 00:00:00

  • Assessment of DNA Epigenetic Modifications.

    abstract::DNA molecules utilize adenine, thymine, cytosine, and guanine for coding genetic information. In addition to these four canonical nucleobases, DNA molecules also contain a variety of modified nucleobases that can control and regulate gene expression and chromosome structure. Elucidating the functions of DNA modificati...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Yuan BF

    更新日期:2020-03-16 00:00:00

  • Ferroptosis: The Greasy Side of Cell Death.

    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


    authors: Friedmann Angeli JP,Miyamoto S,Schulze A

    更新日期:2019-03-18 00:00:00

  • Molecular cytotoxicity mechanisms of allyl alcohol (acrolein) in budding yeast.

    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


    authors: Golla U,Bandi G,Tomar RS

    更新日期:2015-06-15 00:00:00

  • Identification of Quinone Methide Intermediate Resulting from Metabolic Activation of Icaritin in Vitro and in Vivo.

    abstract::Many herbal medicines such as epimedium have been reported to cause adverse effects, and icaritin is the common aglycone of many glucosides in epimedium. Our present work aimed at the clarification of the metabolic activation of icaritin possibly responsible for the adverse effects of epimedium. A quinone methide meta...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Chen Y,Guo X,Ma Y,Hu X,Peng Y,Zheng J

    更新日期:2019-06-17 00:00:00

  • Reactive sulfur species: kinetics and mechanism of the hydrolysis of cysteine thiosulfinate ester.

    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

    pub_type: 杂志文章


    authors: Nagy P,Ashby MT

    更新日期:2007-09-01 00:00:00

  • Interactions of nickel(II) with histones. Stability and solution structure of complexes with CH3CO-Cys-Ala-Ile-His-NH2, a putative metal binding sequence of histone H3.

    abstract::Nickel(II) compounds are established human carcinogens, but the molecular mechanisms underlying their activity are only partially known. One mechanism may include mediation by nickel of promutagenic oxidative DNA damage that depends on Ni(II) binding to chromatin. To characterize such binding at the histone moiety of ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Bal W,Lukszo J,Jezowska-Bojczuk M,Kasprzak KS

    更新日期:1995-07-01 00:00:00

  • Role of metallothionein in zinc(II) and chromium(III) mediated tolerance to carbon tetrachloride hepatotoxicity: evidence against a trichloromethyl radical-scavenging mechanism.

    abstract::The .CCl3 radical generated during the metabolism of CCl4 is readily spin trapped in vivo and in vitro by phenyl N-tert-butylnitrone (PBN) to form the stable PBN/.CCl3 radical adduct, which can then be extracted into organic solvents and detected by ESR spectroscopy. We have used this technique to examine the proposed...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Hanna PM,Kadiiska MB,Jordan SJ,Mason RP

    更新日期:1993-09-01 00:00:00

  • Identification of protein targets of 4-hydroxynonenal using click chemistry for ex vivo biotinylation of azido and alkynyl derivatives.

    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

    pub_type: 杂志文章


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

    更新日期:2008-02-01 00:00:00

  • Identification of adducts formed in the reaction of alpha-acetoxy-N-nitrosopyrrolidine with deoxyribonucleosides and DNA.

    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

    pub_type: 杂志文章


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

    更新日期:2007-04-01 00:00:00