Abstract：
:Exposure of individual histone proteins (H1, H2A, H2B, H3, or H4) and histone octamers (consisting of two molecules each of H2A, H2B, H3, and H4) to hydroxyl radicals, generated by gamma-irradiation, in the presence of O(2) generates protein-bound hydroperoxides in a dose-dependent fashion; this is in accord with previous studies with other proteins. These histone hydroperoxides are stable in the absence of exogenous catalysts (e.g., heat, light, and transition metal ions), but in the presence of these agents decompose rapidly to give a variety of radicals which have been identified by EPR spin trapping. Histone hydroperoxide-derived radicals generated on decomposition of the hydroperoxides with Cu(+) react with both pyrimidine and purine nucleobases. Thus, with uridine the histone hydroperoxide-derived radicals undergo addition across the C(5)-C(6) double bond of the pyrimidine ring to give cross-linked adduct species which have been identified by EPR spectroscopy. HPLC analysis of the products generated on reaction of histone hydroperoxide-derived radicals with 2'-deoxyguanosine, or intact calf thymus DNA, has shown that significant levels of the mutagenic oxidized DNA base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) are formed, with the yield dependent on the individual histone protein, the presence of hydroperoxide functions, and the concentration of metal ion. These studies demonstrate that initial oxidative damage to individual histone proteins or histone octamers can result in the transfer of oxidative damage to associated DNA via the formation and subsequent decomposition of protein hydroperoxides to reactive radicals, and provide a novel route for the formation of mutagenic lesions in DNA.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Luxford C,Dean RT,Davies MJdoi
10.1021/tx000053usubject
Has Abstractpub_date
2000-07-01 00:00:00pages
665-72issue
7eissn
0893-228Xissn
1520-5010pii
tx000053ujournal_volume
13pub_type
杂志文章abstract：:Quantitative structure-activity relationships (QSAR's) are described for the rate of conjugation of a series of fluoronitrobenzenes with cytosolic as well as with two major alpha and mu class enzymes of rat and human liver, viz., glutathione S-transferases (GST) 1-1, 3-3, A1-1, and M1a-1a. For all purified enzymes stu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9501804
更新日期：1996-04-01 00:00:00
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
doi：10.1021/acs.chemrestox.9b00411
更新日期：2020-02-17 00:00:00
abstract：:Hydrophobic and volatile chemicals have proven to be difficult to dose in cell assays. Cosolvents are often needed to dissolve these chemicals in cell culture medium. Moreover, the free concentration of these chemicals in culture medium may diminish over time due to metabolism, evaporation, and nonspecific binding to ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx1002595
更新日期：2010-11-15 00:00:00
abstract：:In May 1981, a massive food-borne intoxication occurred in Spain. The so-called toxic oil syndrome (TOS) was associated with the consumption of aniline-denatured and refined rapeseed oil that was illegally sold as edible olive oil. Fatty acid anilides and fatty acid derivatives of 3-(phenylamino)propane-1,2-diol were ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx990105j
更新日期：1999-12-01 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
pub_type： 杂志文章
doi：10.1021/tx0498206
更新日期：2004-12-01 00:00:00
abstract：:Sex-, species-, and chain length-dependent renal elimination is the hallmark of mammalian elimination of perfluorocarboxylates (PFCAs) and has been extensively studied for almost 30 years. In this review, toxicokinetic data of PFCAs (chain lengths ranging from 4 to 10) in different species are compared with an emphasi...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx200363w
更新日期：2012-01-13 00:00:00
abstract：:Oxidation of the tris(p-carboxyltetrathiaaryl)methyl (TAM) EPR radical probe, TAMa(•), by rat liver microsomes (RLM) + NADPH, or horseradish peroxidase (HRP) + H2O2, or K2IrCl6, led to an intermediate cation, TAMa(+), which was treated with glutathione (GSH), with formation of an adduct, TAMa-SG(•), resulting from the...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx400467p
更新日期：2014-04-21 00:00:00
abstract：:In humans and mice, in utero exposure to inorganic arsenic (iAs) is associated with adverse health outcomes later in life. The contribution of preconception exposure to the adverse outcomes in offspring has never been studied. Here combined in utero and postnatal exposures produce insulin resistance in two collaborati...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00107
更新日期：2019-08-19 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
pub_type： 杂志文章
doi：10.1021/tx050046b
更新日期：2005-08-01 00:00:00
abstract：:The efficacy of DNA-damaging anticancer drugs is highly influenced by cellular DNA repair capacity, and by inhibiting the relevant DNA repair pathway, efficacy of alkylating agents may be increased. Therefore, combining DNA repair inhibitors with anticancer agents that selectively target tumor tissue should improve ca...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx400255f
更新日期：2013-11-18 00:00:00
abstract：:Notopterygium forbesii Boiss (NF) has been used as a traditional Chinese medicine for the treatment of common cold and rheumatism. However, there has been limited research on the biological properties of NF, and the mechanisms of action remain unknown. Here, we aimed to study the mechanism of NF-induced heme oxygenase...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx800301f
更新日期：2008-12-01 00:00:00
abstract：:Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur t...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx9902082
更新日期：2000-03-01 00:00:00
abstract：:The oral dipeptidyl peptidase 1 (DPP1) inhibitor AZD5248 showed aortic binding in a rat quantitative whole-body autoradiography (QWBA) study, and its development was terminated prior to human dosing. A mechanistic hypothesis for this finding was established invoking reactivity with aldehydes involved in the cross-link...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00236
更新日期：2015-10-19 00:00:00
abstract：:Nuclei from human lymphoblast cells grown in culture were treated with [7-14C]-(+/-)-r-7,t-8-dihydroxy-t-9,t-10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (anti-BPDE), and the nucleosomal core histones were isolated for adduct studies by cryogenic fluorescence line narrowing spectroscopy. The four core histones H2A, H2B...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00038a004
更新日期：1994-03-01 00:00:00
abstract：:We have previously reported that the diuretic thiosteroid spironolactone (SPL) inactivates rat liver microsomal cytochromes P450 [P450 (P450 3A and P450 2C11)] in a in a mechanism-based fashion, and we have identified two polar SPL metabolites (SPL-sulfinic acid and -sulfonic acid), formed in a partition ratio of appr...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00024a012
更新日期：1991-11-01 00:00:00
abstract：:2,5-Hexanedione (2,5-HD) is the neurotoxic gamma-diketone metabolite of the industrial solvent n-hexane. Substantial evidence indicates that 2,5-HD reacts with neurofilament protein lysine epsilon-amines to yield 2,5-dimethylpyrrole adducts and that this reaction is critical to the mechanism of toxicity. Alkylpyrroles...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00040a011
更新日期：1994-07-01 00:00:00
abstract：:Reactive nitrogen species (RNS) are produced during infection and inflammation, and the effects of these agents on proteins, DNA, and lipids are well recognized. In contrast, the effects of RNS damaged metabolites are less appreciated. 5-Amino-3-β-(d-ribofuranosyl)-3 H-imidazo-[4,5- d][1,3]oxazine-7-one (oxanosine) an...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00342
更新日期：2019-03-18 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
pub_type： 杂志文章
doi：10.1021/tx060212v
更新日期：2006-12-01 00:00:00
abstract：:Alzheimer's disease, the most common cause of dementia, is at epidemic proportions (15 to 44% depending on age, of those age 65 to 84) in the U.S. and other developed countries but remains relatively rare in undeveloped countries. Surprisingly, solid historical data reveal the epidemic is a creature of the last centur...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/acs.chemrestox.6b00373
更新日期：2017-03-20 00:00:00
abstract：:Genotoxic chemicals act by causing DNA damage, which, if left unrepaired, can have deleterious consequences for cell survival. DNA damage response (DDR) gets activated to repair or mitigate the effects of DNA damage. Histone H2AX and H3 phosphorylation biomarkers (γ-H2AX and p-H3) have attracted great attention as the...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00104
更新日期：2020-08-17 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/acs.chemrestox.8b00349
更新日期：2019-03-18 00:00:00
abstract：:Nitric oxide can be introduced slowly and steadily into aqueous solutions, including cell culture media, over extended periods of time via semipermeable Silastic (a registered trademark of the Dow Corning Corp.) polymer membranes. The rates of introduction are predictable and reproducible and can approach rates of nit...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00036a021
更新日期：1993-11-01 00:00:00
abstract：:Electronic cigarette liquids (e-liquids) with sweetener additives such as sucralose, a synthetic chlorinated disaccharide, are popular among some e-cigarette consumers; sucralose can be added either by the manufacturer or by the consumer. The prevalence of sucralose in commercial e-liquids is not known, nor is the typ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00047
更新日期：2019-06-17 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：:The wide pH range reported for electronic cigarette (ECIG) liquids indicates that nicotine may be present in one or more chemical forms. The nicotine form affects the bioavailability and delivery of nicotine from inhaled products. Protonated nicotine is normally associated with counteranions in tobacco products. The c...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00090
更新日期：2017-08-21 00:00:00
abstract：:The administration of 3'-hydroxyacetanilide, a regioisomer of acetaminophen, to mice failed to produce hepatotoxicity even after the administration of diethyl maleate. In contrast, hepatotoxicity did occur when 3'-hydroxyacetanilide was administered to buthionine sulfoximine pretreated mice. Although the administratio...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00020a014
更新日期：1991-03-01 00:00:00
abstract：:Chloroethylnitrosoureas (CENUs) are bifunctional alkylating agents widely used for the clinical treatment of cancer. They exert anticancer activity by inducing DNA interstrand cross-links (ICLs) within GC base pairs to form dG-dC cross-links. This lesion inhibits DNA double strand separation during replication and tra...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500143b
更新日期：2014-07-21 00:00:00
abstract：:The measurement of metabolites constitutes a useful tool for detection of exposure and in pharmacokinetic studies. Epoxidation with subsequent glutathione conjugation and mercapturic acid formation is an important deactivation pathway for naphthalene, a toxin which presumably causes lung disease. The mercapturic acid ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00033a006
更新日期：1993-05-01 00:00:00
abstract：:Cryogenic (4-10 K) laser-induced vibrationless ground state and vibronic excited state fluorescence emission spectra of the adducts resulting from reaction in vitro of human serum albumin and the carcinogen (+-)-r-7,t-8-dihydroxy-c-9,c-10-epoxy-7,8,9,10- tetrahydrobenzo[a]-pyrene were recorded in order to determine th...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00025a012
更新日期：1992-01-01 00:00:00
abstract：:The DNA alkylating mechanism of PNU-159682 (PNU), a highly potent metabolite of the anthracycline nemorubicin, was investigated by gel-electrophoretic, HPLC-UV, and micro-HPLC/mass spectrometry (MS) measurements. PNU quickly reacted with double-stranded oligonucleotides, but not with single-stranded sequences, to form...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.6b00362
更新日期：2017-02-20 00:00:00
