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) Biochem. J. 338, 553), which suggests a possible protective mechanism against toxic metals for this species. We report the first detailed study of the metal binding properties of F. vesiculosus metallothionein using UV absorption, circular dichroism (CD), and electrospray mass spectral techniques. The overall metal-to-sulfur ratios of this novel algal protein when bound to divalent cadmium and zinc were determined to be Cd(6)S(16) and Zn(6)S(16), respectively. Mixed Cd/Zn species were also formed when Cd(2+) was added to the Zn-containing Fucus metallothionein. Only one conformation was identified at low pH for the native protein. Analysis of the UV absorption, CD, and ESI-MS spectral data recorded during stepwise, acid-induced demetalation supports a two-domain structure for the protein, with two 3-metal binding sites. The data suggest that one of the domains is significantly less stable than the other, and we tentatively propose from the arrangement of cysteines in the sequence that the two domains are M(3)S(7) and M(3)S(9) (where M = Cd(2+) or Zn(2+)). While the M(3)S(9) cluster is known in the beta clusters of crab, lobster, and mammalian metallothioneins, the M(3)S(7) is a hitherto unknown cluster structure. Metallothionein in F. vesiculosus is thought to act as a protective mechanism against incoming toxic metals. The metal binding studies reported are a putative model for metal binding in vivo.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Merrifield ME,Chaseley J,Kille P,Stillman MJdoi
10.1021/tx050206jsubject
Has Abstractpub_date
2006-03-01 00:00:00pages
365-75issue
3eissn
0893-228Xissn
1520-5010journal_volume
19pub_type
杂志文章abstract：:Cyadox is a novel derivative of quinoxaline-1,4-dioxides (QdNOs) with the potential to be developed as a feed additive. However, the pharmacological and toxicological bioactive molecules of cyadox and the molecular mechanism of its pharmacological and toxic actions remain unclear. In the present study, cyadox and its ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00194
更新日期：2018-11-19 00:00:00
abstract：:Arylamines (AAs) and heterocyclic aromatic amines (HAAs) are structurally related carcinogens formed during the combustion of tobacco or cooking of meat. They undergo cytochrome P450 mediated N-hydroxylation to form metabolites which bind to DNA and lead to mutations. The N-hydroxylated metabolites of many AAs also ca...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00418
更新日期：2016-03-21 00:00:00
abstract：:Jay Amin hydroxamic acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA's cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00269
更新日期：2017-12-18 00:00:00
abstract：:A method for the analysis of N-acetylcysteine conjugates of catechol estrogens [catechol estrogen mercapturates (CE SRs)], which are likely to be urinary markers of estrogen-induced tumors, was established in this study. The characteristics of the method that was established were (1) cleanup of urine using the immunoa...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx000182a
更新日期：2000-12-01 00:00:00
abstract：:A new experimental model was designed to study the fate of globin adducts with styrene 7,8-oxide (SO), a metabolic intermediate of styrene and a model electrophilic compound. Rat erythrocytes were incubated with SO at 7 or 22 °C. Levels of specific amino acid adducts in globin were determined by LC/MS analysis of the ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00518
更新日期：2016-04-18 00:00:00
abstract：:Thioredoxin reductase (TR), an NADPH-dependent flavoenzyme that catalyzes the reduction of many disulfide-containing substrates, plays an important role in the cellular response to oxidative stress. Trivalent arsenicals, especially methyl As that contains trivalent arsenic (MAs(III)), are potent noncompetitive inhibit...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0001878
更新日期：2001-03-01 00:00:00
abstract：:The site specifically modified oligonucleotides 5'-d(TCCTCCTG1G2CCTCTC) (I) and 5'-d(CTATG1G2G3TATC) (II) were synthesized with single modified guanine residues at positions G1, G2, or G3, derived from the covalent binding reaction of 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+)-anti-BPDE) with ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9501086
更新日期：1996-01-01 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：:Today much is known about cytochrome P450 (P450) enzymes and their catalytic specificity, but the range of reactions catalyzed by each still continues to surprise. Historically, P450s had been considered to be involved in either the metabolism of xenobiotics or endogenous chemicals, in the former case playing a genera...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.6b00226
更新日期：2017-01-17 00:00:00
abstract：:The hepatotoxicity of Troglitazone (TGZ) has been ascribed to the formation of reactive metabolites, and the primary reactive metabolite of TGZ has been confirmed to be an o-quinone methide. Oxidation of the chromane moiety is also known to produce quinone containing metabolites. Quantum chemical studies have been per...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx200110h
更新日期：2011-07-18 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
abstract：:Pyridoxamine (PM) is an effective inhibitor of the formation of the carcinogen acrylamide (AA) from its precursors in low-moisture model systems. Although AA is widely assumed to act by scavenging carbonyl compounds, no alternative pathways have to date been explored. In this work, we found AA to directly react with P...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx100293y
更新日期：2011-03-21 00:00:00
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
doi：10.1021/tx00030a010
更新日期：1992-11-01 00:00:00
abstract：:The term class effect has gained in use to describe a side effect including toxicity common to a series of drugs. There is no definition of what constitutes a class effect, and it is not applied against a rigid set of criteria.Thus, the finding of toxicity in one of a series of drugs can raise the concern of a class e...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx100408v
更新日期：2011-04-18 00:00:00
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
doi：10.1021/acs.chemrestox.7b00196
更新日期：2017-10-16 00:00:00
abstract：:Amyloid-β plaques and oxidative stress are the major hallmarks of Alzheimer's disease. Our previous study found that the heme-Aβ complex enhanced the catalytic effect of free heme on protein tyrosine nitration in the presence of hydrogen peroxide (H2O2) and nitrite (NO2-). Y10 in Aβ could be the first target to be nit...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.6b00447
更新日期：2017-04-17 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
pub_type： 杂志文章
doi：10.1021/tx0502387
更新日期：2005-11-01 00:00:00
abstract：:The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc st...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx990156g
更新日期：2000-01-01 00:00:00
abstract：:Dysregulation in the expression of microRNAs (miRNAs), single-stranded RNAs which regulate gene expression, has been associated with diseases such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), although their cellular origin has not been explored. Thus, the focus of this work was to study expressi...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00330
更新日期：2018-06-18 00:00:00
abstract：:The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with a slight increased cancer risk. Previously, we showed that equilenin, a minor component of Premarin (Wyeth-Ayerst), was metab...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx980217v
更新日期：1999-02-01 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
pub_type： 杂志文章
doi：10.1021/tx050328b
更新日期：2006-03-01 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：:Premarin (Wyeth-Ayerst) is the estrogen replacement treatment of choice and continues to be one of the most widely dispensed prescriptions in the United States. In addition to endogenous estrogens, Premarin contains unsaturated estrogens including equilenin. We synthesized the catechol metabolite of equilenin, 4-hydro...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx970181r
更新日期：1998-02-01 00:00:00
abstract：:Cytochrome P-450 enzymes have been postulated to oxidize amines through a variety of mechanisms. One of the means of distinguishing among potential pathways involves the use of kinetic hydrogen isotope effects: low isotope effects are characteristic of aminium radical mechanisms while high values are consistent with h...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00013a004
更新日期：1990-01-01 00:00:00
abstract：:Furanoid 8-epidiosbulbin E acetate (EEA) is one of the most abundant diterpenoid lactones in herbal medicine Dioscorea bulbifera L. (DB). Our early work proved that EEA could be metabolized to EEA-derived cis-enedial (EDE), a reactive intermediate, which is required for the hepatotoxicity observed in experimental anim...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00016
更新日期：2020-07-20 00:00:00
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
doi：10.1021/acs.chemrestox.9b00372
更新日期：2020-03-16 00:00:00
abstract：:O6-Benzyl-2'-deoxyguanosine is a potential antitumor drug modulator that is intended to reduce or eliminate O6-alkylguanine-DNA alkyltransferase activity in tumors prior to treatment with genotoxic chemotherapeutic alkylating agents. The rationale for using this compound instead of the more active O6-benzylguanine and...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00042a008
更新日期：1994-11-01 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
pub_type： 杂志文章
doi：10.1021/tx050046b
更新日期：2005-08-01 00:00:00
abstract：:Human breast milk is considered as the best and ideal form of nutrition for infants. However, food contaminants such as mycotoxins, which may be transferred from maternal blood to milk, are poorly described. Mycotoxins are a major group of natural toxins frequently detected in foods. Here, we review the current state-...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.6b00125
更新日期：2016-07-18 00:00:00
abstract：:Rutaevin is one of the major bioactive constituents isolated from Evodia rutaecarpa, a well-known herbal medicine that has been widely prescribed for the treatment of gastrointestinal disorders in China. However, oral administration of rutaevin has been shown to cause hepatotoxicity in mice. Bioactivation was suggeste...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00475
更新日期：2020-12-21 00:00:00
