Abstract:
: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.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Lord HL,Josephy PD,Snieckus VAdoi
10.1021/tx00015a002subject
Has Abstractpub_date
1990-05-01 00:00:00pages
195-8issue
3eissn
0893-228Xissn
1520-5010journal_volume
3pub_type
杂志文章abstract::Double-strand breaks are widely accepted to be the most toxic form of DNA damage. Molecules that produce double-strand breaks via a single chemical event are typically very cytotoxic and far less common than those that form single-strand breaks. It was recently reported that a commonly formed C4'-radical produces doub...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00032
更新日期:2015-04-20 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
pub_type: 杂志文章
doi:10.1021/tx0001272
更新日期:2000-12-01 00:00:00
abstract::Topoisomerase II is an essential nuclear enzyme involved in regulating DNA topology to facilitate replication and cell division. Disruption of topoisomerase II function by chemotherapeutic agents is in use as an effective strategy to fight cancer. Etoposide is an anticancer therapeutic that disrupts the catalytic cycl...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00209
更新日期:2016-09-19 00:00:00
abstract::The carcinogen 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) alkylates DNA at dGuo, dAdo, and dCyd. dCyd adducts, formed in small amounts, elute near the more abundant dGuo adducts. We isolated the dCyd adducts formed with dCMP. Each BPDE enantiomer forms three major adducts with dCMP, two...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0340201
更新日期:2004-04-01 00:00:00
abstract::This study addresses the detection and characterization of the modification of human serum albumin (HSA) by amoxicillin (AX) in ex vivo samples from healthy subjects under oral amoxicillin administration (acute intake of 1 g every 8 h for 48 h). To reach this goal, we used an analytical strategy based on targeted and ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500210e
更新日期:2014-09-15 00:00:00
abstract::Acetaminophen (AP) is a popularly recommended over-the-counter analgesic-antipyretic in clinical use. However, the drug is handicapped by the occurrence of hepatotoxic insult following acute ingestion. Consequently, AP-induced hepatotoxicity is often implicated in accidental or suicidal overdose. In the current study,...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00392
更新日期:2020-02-17 00:00:00
abstract::Drug-induced myocardial infarction (DIMI) is one of the most serious adverse drug effects that often lead to death. Therefore, the identification of DIMI at the early stages of drug development is essential. For this purpose, the in vitro testing and in silico prediction of interactions between drug-like substances an...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500147d
更新日期:2014-07-21 00:00:00
abstract::High-throughput screening (HTPS) assays to detect inhibitors of thyroperoxidase (TPO), the enzymatic catalyst for thyroid hormone (TH) synthesis, are not currently available. Herein, we describe the development of a HTPS TPO inhibition assay. Rat thyroid microsomes and a fluorescent peroxidase substrate, Amplex UltraR...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400310w
更新日期:2014-03-17 00:00:00
abstract::A correct estimate of ligand binding modes and a ratio of their occupancies is crucial for calculations of binding free energies. The newly developed method BLUES combines molecular dynamics with nonequilibrium candidate Monte Carlo. Nonequilibrium candidate Monte Carlo generates a plethora of possible binding modes a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00030
更新日期:2019-07-15 00:00:00
abstract::Metabolic bioactivation, glutathione depletion, and covalent binding are the early hallmark events after acetaminophen (APAP) overdose. However, the subsequent metabolic consequences contributing to APAP-induced hepatic necrosis and apoptosis have not been fully elucidated. In this study, serum metabolomes of control ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800464q
更新日期:2009-04-01 00:00:00
abstract::Nuclear magnetic resonance (NMR) spectroscopy has traditionally been considered as an indispensable tool in elucidating structures of metabolites. With the advent of Fourier transform (FT) spectrometers, along with improvements in software and hardware (such as high-field magnets, cryoprobes, versatile pulse sequences...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800251p
更新日期:2009-02-01 00:00:00
abstract::PAHs (polycyclic aromatic hydrocarbons) are suspect lung cancer carcinogens that must be metabolically converted into DNA-reactive metabolites. P4501A1/P4501B1 plus epoxide hydrolase activate PAH to (+/-)- anti-benzo[ a]pyrene diol epoxide ((+/-)- anti-BPDE), which causes bulky DNA adducts. Alternatively, aldo-keto re...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700404a
更新日期:2008-05-01 00:00:00
abstract::The group of perylene quinone-type Alternaria toxins contains several congeners with epoxide groups, for example, altertoxin II (ATX II) and stemphyltoxin III (STTX III). Recent studies in our laboratory have disclosed that the epoxide moieties of ATX II and STTX III are reduced to alcohols in human colon Caco-2 cells...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400366w
更新日期:2014-02-17 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::Isoeugenol is widely used by the cosmetic and fragrance industries, but it also represents a known cause of skin sensitization adverse effects. Although devoid of a structural alert, isoeugenol has been classified as prehapten in virtue of the presence of a pre-Michael acceptor domain. Isoeugenol oxidation could theor...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00501
更新日期:2020-04-20 00:00:00
abstract::The urine from mice exposed to styrene vapors (600 and 1200 mg/m(3), 6 h) was analyzed for ring-oxidized metabolites of styrene. To facilitate the identification of metabolites in urine, the following potential metabolites were prepared: 2-, 3-, and 4-vinylphenol (2-, 3-, and 4-VP), 4-vinylpyrocatechol, and 2-, 3-, an...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9004192
更新日期:2010-01-01 00:00:00
abstract::The use of powerful analytical technologies to detect endogenous carbonyls formed as byproducts of oxidative cell injury has revealed that these species contribute to many human diseases. As electrophiles, they are attacked by reactive centers in cell macromolecules to form adducts, the levels of which serve as useful...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700399q
更新日期:2008-04-01 00:00:00
abstract::The risk of potential human exposure to mixed nanomaterials in consumer, occupational, and medicinal settings is increasing as nanomaterials enter both the workplace and the marketplace. In this study, we investigated the toxicity of mixed engineered carbon black (ECB) and maghemite iron oxide (Fe(2)O(3)) nanoparticle...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100307h
更新日期:2010-12-20 00:00:00
abstract::Sulfhydration by a hydrogen sulfide anion and electrophile thiolation by reactive sulfur species (RSS) such as persulfides/polysulfides (e.g., R-S-SH/R-S-Sn-H(R)) are unique reactions in electrophilic signaling. Using 1,2-dihydroxynaphthalene-4-thioacetate (1,2-NQH2-SAc) as a precursor to 1,2-dihydroxynaphthalene-4-th...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500416y
更新日期:2015-05-18 00:00:00
abstract::Electrochemical oxidation of drug molecules is a useful tool to generate several different types of metabolites. In the present study we developed a model system involving electrochemical oxidation followed by characterization of the oxidation products and their propensity to modify peptides. The CB1 antagonist rimona...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx500255r
更新日期:2014-10-20 00:00:00
abstract::The reduced transcriptomic approach allows full dose range testing of hundreds of chemicals or mixtures using human cells or zebrafish embryos. Points of departure of genes and pathways can be used for potency ranking and to classify chemicals by disrupted biological pathways. ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00104
更新日期:2018-07-16 00:00:00
abstract::3-Alkyl-1,2,3-oxadiazolinium ions 1 have been proposed as reactive intermediates in the activation of (2-hydroxyethyl)nitrosamines. The reaction of 3-methyl-1,2,3-oxadiazolinium tosylate (1a), 2-ethyl-1-methoxy-2-phenyldiazenium tetrafluoroborate (3), and 3-phenyl-1,2,3-oxadiazolinium triflate (1b) with thiols was inv...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00048a001
更新日期:1995-09-01 00:00:00
abstract::Reactive oxygen species can induce the formation of tandem DNA lesions. We recently showed that the treatment of calf thymus DNA with Cu2+/H2O2/ascorbate could result in the efficient formation of a tandem lesion where a 5,6-dihydroxy-5,6-dihydrothymidine (or thymidine glycol) is situated on the 5' side of an 8-oxo-7,...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8003449
更新日期:2009-03-16 00:00:00
abstract::In vitro techniques have been utilized to investigate the microsomal enzymes involved in the metabolism of lauric acid and to establish conditions in which it can be used as a model substrate for both cytochrome P450 4A and cytochrome P450 2E1 in human liver microsomes. Studies of enzyme kinetics of lauric acid omega-...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00042a018
更新日期:1994-11-01 00:00:00
abstract::Interstrand cross-links are minor components of the collection of products formed in DNA by ionizing radiation. Through their formation by other damaging agents, it is known that interstrand cross-links exert significant effects on replication and transcription. The structures of DNA interstrand cross-links produced a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx7002307
更新日期:2007-11-01 00:00:00
abstract::Copper is a physiologically important, redox-active metal that may be involved in endogenous DNA damage and mutagenesis. To understand the factors that affect the location and quantity of copper-induced oxidative DNA damage in cells, we used the 5S rDNA nucleosome as a model to assess the effect of chromatin structure...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0002278
更新日期:2001-04-01 00:00:00
abstract::DNA nucleobases are the prime targets for chemical modifications by endogenous and exogenous electrophiles. Alkylation of the N7 position of guanine and adenine in DNA triggers base-catalyzed imidazole ring opening and the formation of N5-substituted formamidopyrimidine (N5-R-FAPy) lesions. Me-FAPy-dG adducts induced ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00392
更新日期:2017-01-17 00:00:00
abstract::S-(1,2-Dichlorovinyl)-L-cysteine (DCVC), a mutagenic and nephrotoxic metabolite of trichloroethylene, is bioactivated to S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS) and chlorothioketene and/or 2-chlorothionoacetyl chloride by cysteine conjugate S-oxidase (S-oxidase) and cysteine conjugate beta-lyase (beta-lyase...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900219x
更新日期:2009-09-01 00:00:00
abstract::Xenobiotics may activate the estrogen receptor, resulting in alteration of normal endocrine functions in animals and humans. Consequently, this necessitates development of assay end points capable of identifying estrogenic xenobiotics. In the present study, we screened the potential estrogenicity of chemicals via thei...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002089
更新日期:2014-08-18 00:00:00
abstract::Proton pump inhibitors (PPIs) are extensively used for the treatment of gastric acid-related disorders. PPIs appear to be well tolerated and almost have no short-term side effects. However, the clinical adverse reactions of long-term PPI usage are increasingly reported in recent years. So far, there is no study that e...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5003782
更新日期:2015-03-16 00:00:00