Abstract:
:1,3-Butadiene (BD) is a high-volume industrial chemical and a common environmental pollutant. Although BD is classified as a "probable human carcinogen", only limited evidence is available for its tumorigenic effects in occupationally exposed populations. Animal studies show a surprisingly high sensitivity of mice to the carcinogenic effects of BD compared to rats (approximately 10(3)-fold), making interspecies extrapolations difficult. Identification and quantitation of specific BD-induced DNA adducts are important for improving our understanding of the mechanisms of BD biological effects and for explaining the observed species differences. Covalent binding of BD to DNA is probably due to its two epoxy metabolites: 3,4-epoxy-1-butene (EB) and 1,2:3,4-diepoxybutane (DEB). Both EB and DEB are direct mutagens producing frameshift and point mutations at both A:T and G:C base pairs. DEB is 100 times more mutagenic than EB and is found in quantity only in tissues of the most sensitive species (mouse). This has led to the suggestion that the higher sensitivity of mice to BD could be due to greater exposure to DEB. The present work was initiated in order to isolate and structurally characterize DEB-induced adenine adducts. The adducts were formed by reacting DEB with free adenine (Ade), 2'-deoxyadenosine (2'-dAdo), and calf thymus DNA followed by HPLC separation and analysis of the products by UV spectrophotometry, electrospray ionization mass spectrometry, and nuclear magnetic resonance. The adenine reaction resulted in three products which were identified as N-3-, N-7-, and N-9-(2'-hydroxy-3',4'-epoxybut-1'-yl)adenine. These adducts underwent acid-catalyzed hydrolysis to their corresponding (2',3',4'-trihydroxybut-1'-yl)adenines upon heating or storage. The 2'-dAdo reaction with DEB followed by acid hydrolysis yielded a single adduct, N6-(2',3',4'-trihydroxybut-1'-yl)adenine (N6-DEB-Ade). N-3-DEB-Ade and N6-DEB-Ade were also found in hydrolysates of calf thymus DNA exposed to DEB. The amounts of N-3-DEB-Ade (13/10(3) normal Ade) and N6-DEB-Ade (5/10(3) normal Ade) were slightly lower than those of the corresponding EB-induced adducts in similar experiments, suggesting comparable reactivity of the two epoxy metabolites of BD toward adenine in DNA. The findings of this study provide a basis for future analyses of BD-induced adenyl DNA adducts in vitro and in vivo.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Tretyakova N,Sangaiah R,Yen TY,Gold A,Swenberg JAdoi
10.1021/tx9700681subject
Has Abstractpub_date
1997-10-01 00:00:00pages
1171-9issue
10eissn
0893-228Xissn
1520-5010pii
tx9700681journal_volume
10pub_type
杂志文章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::The oxidation state of intracellular chromium has been determined directly in mammalian lung cells exposed to mutagenic and carcinogenic chromium compounds. Microprobe X-ray absorption spectroscopy (XAS) experiments on single V79 Chinese hamster lung cells showed that Cr(VI) and Cr(V) complexes were reduced completely...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970010m
更新日期:1997-05-01 00:00:00
abstract::1-{4-[(4-Phenyl-5-trifluoromethyl-2-thienyl)methoxy]benzyl}azetidine-3-carboxylic acid (MRL-A) is a potent sphingosine-1-phosphate-1 receptor agonist, with potential application as an immunosuppressant in organ transplantation or for the treatment of autoimmune diseases. When administered orally to rats, radiolabeled ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300017s
更新日期:2012-07-16 00:00:00
abstract::The genotoxicity of the dihydrofurans aflatoxin B1 (AFB1), aflatoxin G1 (AFG1), and sterigmatocystin (STG) was examined in a bacterial system in which the induction of SOS repair is monitored with the umuC gene linked to a lacZ reporter gene in plasmid pSK1002. Human liver microsomal cytochrome P-450NF oxidized the di...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00008a008
更新日期:1989-03-01 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
pub_type: 杂志文章
doi:10.1021/tx050206j
更新日期:2006-03-01 00:00:00
abstract::A predominant pathway of xenobiotic-induced toxicity is initiated by bioactivation. Characterizing reactive intermediates will provide information on the structure of reactive species, thereby defining a potential bioactivation mechanism. Because most reactive metabolites are not stable, it is difficult to detect them...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200033v
更新日期:2011-05-16 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
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00352
更新日期:2019-11-18 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
pub_type: 杂志文章
doi:10.1021/tx049697i
更新日期:2005-03-01 00:00:00
abstract::We have recently shown that dithiocarbamate (DC) disulfides inhibit proteolytic processing of the caspase-3 proenzyme in Jurkat T lymphocytes treated with anti-CD95 (Fas/APO-1) antibody. Because the processing can be accomplished by caspase activity, we investigated the effect of DC disulfides, such as disulfiram (DSF...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970131m
更新日期:1997-12-01 00:00:00
abstract::3-(2-Deoxy-beta-D-erythro-pentofuranosyl)-6-hydroxy-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one is formed in low yield by the reaction of acrolein with 2'-deoxyguanosine. The nucleoside and an oligodeoxynucleotide containing it have been synthesized. For preparation of the nucleoside 2'-deoxyguanosine was alkyla...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010181y
更新日期:2002-05-01 00:00:00
abstract::Arsenic is one of the inorganic pollutants typically found in natural waters, and its toxic effects on the human body are currently of great concern. For this reason, the search for detoxifying agents that can be used in a so-called "chelation therapy" is of primary importance. However, to the aim of finding the therm...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00506
更新日期:2020-04-20 00:00:00
abstract::A liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) method for the measurement of aflatoxin biomarkers in urine has been developed and validated. The two major aflatoxin-DNA adducts formed in rat tissues, aflatoxin N(7)-guanine and its imidazole ring opened derivative, 8,9-dihydro-8-(2,6-diami...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010063a
更新日期:2001-07-01 00:00:00
abstract::The growth-promoting effects of estrogens in hormone-dependent tumor tissues involve receptor-mediated pathways that are well-recognized; however, the role of estrogens in tumor initiation remains controversial. Estrogen metabolites, primarily the catechol estrogens (CE's), have been implicated in tumor initiation via...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx980128i
更新日期:1999-03-01 00:00:00
abstract::Epidemiological evidence suggests a lower incidence of Parkinson's disease in smokers than in nonsmokers. This evidence, together with the lower levels of brain monoamine oxidase (MAO) activity in smokers and the potential neuroprotective properties of MAO inhibitors, prompted studies which led to the isolation and ch...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000224v
更新日期:2001-05-01 00:00:00
abstract::Bisphenol A (BPA) is ubiquitous in the environment and is reported to be present at high concentrations in placental tissue, where its presence raises concerns over its potential to disrupt placental function. This report investigates how BPA interferes with the survival of human choriocarcinoma BeWo cells (a model of...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00093
更新日期:2015-09-21 00:00:00
abstract::The N-reduction of the centrally acting alpha 2-adrenoreceptor agonist guanoxabenz (Benzérial), an N-hydroxyamidinohydrazone, to the amidinohydrazone guanabenz (Wytensin, Hipten, Rexitene) by microsomal fractions from rabbits, pigs and humans has been detected in vitro. The conversion rates with rabbit microsomal frac...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9502047
更新日期:1996-06-01 00:00:00
abstract::All pesticides must go through a rigorous risk assessment process in order to show that they are safe for use.With respect to dermal risk assessment for re-entry workers, the absorption value applied to predict systemic dose from this external exposure is obtained by testing liquid forms of the pesticide in vivo and/o...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500509z
更新日期:2015-02-16 00:00:00
abstract::The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum and in vitro in PC12 cells and human cultured fibroblasts and glial cells. The in vi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002223
更新日期:2014-08-18 00:00:00
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
doi:10.1021/tx00047a007
更新日期:1995-07-01 00:00:00
abstract::The biological response of bronchial epithelial cells to particles is associated with a sequestration of cell metal by the particle surface and a subsequent disruption in host iron homeostasis. The macrophage is the cell type resident in the respiratory tract that is most likely to make initial contact with inhaled pa...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00301
更新日期:2019-09-16 00:00:00
abstract::This study was designed to distinguish and evaluate the contribution of reactive metabolite and reactive oxygen species as the mechanism of metabolism-dependent valproic acid-induced in vitro cytotoxicity. The involvement of reactive oxygen species in the mechanism of in vitro cytotoxicity was examined by the addition...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9801864
更新日期:1999-04-01 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
pub_type: 杂志文章
doi:10.1021/tx0601861
更新日期:2007-01-01 00:00:00
abstract::Hydrazyl radical intermediates have been suggested as important intermediates in the biochemistry of hydrazides and hydrazines. Although spin-trapping studies have intercepted those species previously, there has been no report of the direct observation of the unstable hydrazyl radicals of isoniazid and iproniazid. We ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0341759
更新日期:2004-02-01 00:00:00
abstract::(R)-Thalidomide was oxidized to 5-hydroxythalidomide and 5'-hydroxythalidomide by NADPH-fortified liver microsomes from humans and monkeys. (R)-Thalidomide was hydroxylated more efficiently than (S)-thalidomide. Recombinant human P450s 3A4, 3A5, and 3A7 and monkey P450s 3A8 and 3A5 (coexpressed with NADPH-P450 reducta...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900367p
更新日期:2010-06-21 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
pub_type: 杂志文章
doi:10.1021/tx700252n
更新日期:2007-12-01 00:00:00
abstract::Chloroprene (2-chloro-1,3-butadiene, 1) is an important industrial chemical, which is carcinogenic in experimental animals and possibly in humans. It is metabolized to the monoepoxides, 2-chloro-2-ethenyloxirane (2a,b) and (1-chloroethenyl)oxirane (3a,b), together with electrophilic chlorinated aldehydes and ketones. ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx034107m
更新日期:2003-10-01 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
pub_type: 杂志文章
doi:10.1021/tx050134w
更新日期:2005-10-01 00:00:00
abstract::alpha-Sulfate trans-tamoxifen and alpha-sulfate cis-tamoxifen were synthesized as proposed active metabolites of tamoxifen that react with DNA. alpha-Acetoxytamoxifen was prepared as a model-activated form to produce a reactive carbocation. Calf thymus DNA was reacted with alpha-hydroxytamoxifen or the activated forms...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960114h
更新日期:1997-02-01 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
pub_type: 杂志文章
doi:10.1021/tx700434v
更新日期:2008-04-01 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
pub_type: 杂志文章
doi:10.1021/tx049821y
更新日期:2004-12-01 00:00:00