Abstract：
:Increasing exposure of biological systems to large amounts of polycyclic aromatic hydrocarbons is of great public concern. Organisms have an array of biological defense mechanisms, and it is believed that mucosal gel (which covers the respiratory system, the gastrointestinal tract, etc.) provides an effective chemical shield against a range of toxic materials. However, in this work, we demonstrate, for the first time, that, upon complexation of polyaromatic hydrocarbons with mucins, enhanced bioavailability and, therefore, toxicity are obtained. This work was aimed to demonstrate how complexation of various highly hydrophobic polycyclic aromatic hydrocarbons with representative mucin glycoprotein could lead to the formation of previously undescribed materials, which exhibit increased toxicity versus pristine polycyclic aromatic hydrocarbons. In the present work, we show that a representative mucin glycoprotein, bovine submaxillary mucin, has impressive and unprecedented capabilities of binding and solubilizing water-insoluble materials in physiological solution. The complexes formed between the mucin and a series of polycyclic aromatic hydrocarbons were comprehensively characterized, and their toxicity was evaluated by both in vivo and in vitro assays. In addition, the bioavailability and membrane-penetration capabilities were tested using an internalization assay. Our results provide, for the first time, evidence of an unknown route by which hydrophobic materials may achieve higher bioavailability, penetrating some of the biological defense systems, in the form of water-soluble complexes with mucosal proteins.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Drug E,Landesman-Milo D,Belgorodsky B,Ermakov N,Frenkel-Pinter M,Fadeev L,Peer D,Gozin Mdoi
10.1021/tx100426ssubject
Has Abstractpub_date
2011-03-21 00:00:00pages
314-20issue
3eissn
0893-228Xissn
1520-5010journal_volume
24pub_type
杂志文章abstract：:Nitrogen mustards (NM) are an important class of chemotherapeutic drugs used in the treatment of malignant tumors. The accepted mechanism of action of NM is through the alkylation of DNA bases. NM-adducts block DNA replication in cancer cells by forming cytotoxic DNA interstrand cross-links. We previously characterize...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00012
更新日期：2020-04-20 00:00:00
abstract：:Thioureas are oxygenated by flavin-containing monooxygenases (FMOs), forming reactive sulfenic and/or sulfinic acids. Sulfenic acids can reversibly react with GSH and drive oxidative stress through a redox cycle. For this reason, thiourea S-oxygenation is an example of FMO-dependent bioactivation of a xenobiotic. Func...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx034253s
更新日期：2004-05-01 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：: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
doi：10.1021/tx700347w
更新日期：2008-02-01 00:00:00
abstract：:Protein glutathionylation is an important protein post-translational modification associated with oxidative stress, in which the thiol groups of cysteine residues react with glutathione and form disulfide bonds. Glutathionylation has been shown to affect protein structure and modulate protein function, and is implicat...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx5000359
更新日期：2014-05-19 00:00:00
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
doi：10.1021/tx00030a016
更新日期：1992-11-01 00:00:00
abstract：:Exposure to inorganic arsenic (iAs) induces cancer in human lungs, urinary bladder, skin, kidney, and liver, with the majority of deaths from lung and bladder cancer. To date, cancer risk assessments for iAs have not relied on mechanistic data, as we have lacked sufficient understanding of arsenic's pharmacokinetics a...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx900343d
更新日期：2010-02-15 00:00:00
abstract：:2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed during the cooking of meats. PhIP is a potential human carcinogen: it undergoes metabolic activation to form electrophilic metabolites that bind to DNA and proteins, including serum albumin (SA). The structures of Ph...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx300253j
更新日期：2012-10-15 00:00:00
abstract：:The deposition and transport of toxicants on pulmonary surfactant are important processes in human health and medical care. We have introduced classical density functional theory (CDFT) to provide insight into this process. Nine typical toxicants in PM2.5 were considered, and their free energy and structural informati...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00272
更新日期：2018-12-17 00:00:00
abstract：:The increasing use of fullerene nanomaterials has prompted widespread concern over their biological effects. Herein, we have studied the phototoxicity of gamma-cyclodextrin bicapped pristine C 60 [(gamma-CyD) 2/C 60] and its water-soluble derivative C 60(OH) 24 toward human keratinocytes. Our results demonstrated that...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx800056w
更新日期：2008-05-01 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：:So far, there is limited information on biotransformation mechanisms and products of polar contaminants in freshwater crustaceans. In the present study, metabolites of biocides and pharmaceuticals formed in Gammarus pulex and Daphnia magna were identified using liquid chromatography-high resolution mass spectrometry. ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx300457f
更新日期：2013-03-18 00:00:00
abstract：:Epidemiological studies have implicated a role for airborne particulates of <2.5 microm diameter in the development/exacerbation of chronic cardiopulmonary disease; however, specific pathogenic mechanisms and the etiological significance of particle physicochemical properties remain unresolved. Using a microporous alu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx049893p
更新日期：2004-10-01 00:00:00
abstract：:The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was investigated in five human volunteers given a dietary equivalent of 14C-labeled MeIQx. The amount of the dose excreted in urine ranged from 20.2% to 58.6%, with unmetabolized MeIQx accounting for 0.7-2.8% of the dose. Five principal metabolite...
journal_title：Chemical research in toxicology
pub_type： 临床试验,杂志文章
doi：10.1021/tx9701891
更新日期：1998-03-01 00:00:00
abstract：:Alcohol consumption is associated with an increased risk of several types of malignancy by mechanisms that remain to be elucidated. Most of the ingested ethanol is converted to acetaldehyde but the formation of free radical metabolites such as the 1-hydroxyethyl radical has been also demonstrated to occur in vitro and...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9800351
更新日期：1998-08-01 00:00:00
abstract：:Nanoparticles can reach the blood and cause inflammation, suggesting that nanoparticles-endothelial cells interactions may be pathogenically relevant. We evaluated the effect of titanium dioxide nanoparticles (TiO₂) on proliferation, death, and responses related with inflammatory processes such as monocytic adhesion a...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx200551u
更新日期：2012-04-16 00:00:00
abstract：:The activity of three metabolically activated methylating agents, N-methyl-N-(acetoxymethyl)nitrosamine (DMN-OAc), methylnitrosourethane (MNUT), and (methylazoxy)methanol acetate (MAM-Ac), were determined in cell culture by using a P388 cell growth rate inhibition assay. Experiments were conducted with normal P388 cel...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00011a004
更新日期：1989-09-01 00:00:00
abstract：:Sulfamethoxazole (SMX) is an important antibiotic in the management of patients with cystic fibrosis, but allergic reactions may develop thus restricting therapy. The aim of this study was to utilize drug (metabolite) antigens to diagnose SMX-mediated allergic reactions in patients with cystic fibrosis. Lymphocytes fr...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx100151v
更新日期：2010-06-21 00:00:00
abstract：:The hepatic metabolism of microcystins (MCs), potent cyclic peptide hepatotoxins produced by cyanobacteria, was studied by i.p. injection in mice and rats. An immunoaffinity purification method using an anti-MC-LR monoclonal antibody showed a remarkable effect on the removal of contaminants in the hepatic cytosol and ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx960085a
更新日期：1996-12-01 00:00:00
abstract：:A well-defined silica nanoparticle model system was developed to study the effect of the size and structure of aggregates on their membranolytic activity. The aggregates were stable and characterized using transmission electron microscopy, dynamic light scattering, nitrogen adsorption, small-angle X-ray scattering, in...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx2002178
更新日期：2011-11-21 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：:The neurotrophic factor pleiotrophin (PTN) is upregulated in different brain areas after the administration of different drugs of abuse, including psychostimulants. PTN has been shown to prevent cocaine-induced cytotoxicity in NG108-15 and PC12 cells. We previously demonstrated that specific phosphoproteins related to...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00130
更新日期：2015-07-20 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：:Recent reports by Galeazzi and co-workers demonstrated the susceptibility of Abeta(1-42) to undergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formed dityrosine cross-links in Abeta(1-40) using these enzymatic conditions as well as a copper-H(2)O(2) method. The efficiency of dityrosi...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx025666g
更新日期：2003-04-01 00:00:00
abstract：:N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1) is an orally administrated drug widely used in the chemotherapy of chronic lymphocytic leukemia. We have recently described a new metabolic path for the decomposition of 1 in human gastric juice based on its reactions with saliva-derived thiocyanate io...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx980122t
更新日期：1998-11-01 00:00:00
abstract：:An N-methyl-N-nitrosourea (MNU) moiety [CH3N(N=O)C(=O)NH-] linked to the C4'-position of the 5-substituted phenyl ring of phenyl neutral red (PNR), 2-methyl-3-amino-5-[p-[[2-[(N-nitroso-N-methylcarbamoyl)amino]ethy l] carbamoyl]phenyl]-7-(dimethylamino)phenazenium chloride (MNU-PNR), has been synthesized as an approac...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx960007n
更新日期：1996-09-01 00:00:00
abstract：:Nitric oxide (NO(•); nitrogen monoxide) is known to be a critical regulator of cell and tissue function through mechanisms that utilize its unique physicochemical properties as a small and uncharged free radical with limited reactivity. Here, the basic chemistry and biochemistry of NO(•) are summarized through the des...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/tx300042g
更新日期：2012-05-21 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：: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：:Finger 3 of transcription factor IIIA of Xenopus laevis was synthesized and constituted with Zn(2+) or Cd(2+). The C-block element of the internal control region of the promoter of the 5S rRNA gene binds to the Zn-F3 and Cd-F3 with dissociation constants of 2.6 x 10(-5) and 1.5 x 10(-4) M, respectively. According to N...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx030057+
更新日期：2004-07-01 00:00:00
