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    5432 results match your criteria Chemical Research in Toxicology [Journal]

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    Influence of UGT2B10 genotype on urinary excretion of NNAL-N-glucuronide by African American smokers.
    Chem Res Toxicol 2018 Feb 20. Epub 2018 Feb 20.
    At similar smoking levels African American's lung cancer risk is as much as twice that of whites. We hypothesized that racial/ethnic differences in UDP-glucuronosyltransferase (UGT)-catalyzed glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a detoxication pathway for the tobacco-specific lung carcinogen NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone), may contribute to this variable risk. UGT2B10 catalyzes NNAL N-glucuronidation and a UGT2B10 splice variant is common among African Americans. Read More

    Quasi-SMILES-Based Nano-Quantitative Structure-Activity Relationship Model to Predict the Cytotoxicity of Multiwalled Carbon Nanotubes to Human Lung Cells.
    Chem Res Toxicol 2018 Feb 19. Epub 2018 Feb 19.
    Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe , Campus E 7.1, D-66123 Saarbruecken, Germany.
    Quantitative structure-activity relationship (QSAR) models for nanomaterials (nano-QSAR) were developed to predict the cytotoxicity of 20 different types of multiwalled carbon nanotubes (MWCNTs) to human lung cells by using quasi-SMILES. The optimal descriptors, recorded as quasi-SMILES, were encoded to represent the physicochemical properties and experimental conditions for the MWCNTs from 276 data records collected from previously published studies. The quasi-SMILES used to build the optimal descriptors were (i) diameter, (ii) length, (iii) surface area, (iv) in vitro toxicity assay, (v) cell line, (vi) exposure time, and (vii) dose. Read More

    Application of in Vitro T Cell Assay Using Human Leukocyte Antigen-Typed Healthy Donors for the Assessment of Drug Immunogenicity.
    Chem Res Toxicol 2018 Feb 14. Epub 2018 Feb 14.
    MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool , Sherrington Building, Ashton Street, Liverpool L69 3GE, England.
    It is unclear whether priming of naïve T cells to drugs is detectable in healthy human donors expressing different human leukocyte antigen (HLA) alleles. Thus, we examined T cell priming with drugs associated with HLA risk alleles and control compounds in 14 HLA-typed donors. Nitroso sulfamethoxazole and piperacillin activated T cells from all donors, whereas responses to carbamazepine and oxypurinol were only seen in donors expressing HLA-B*15:02 and HLA-B*58:01, respectively. Read More

    Analysis of Urinary Eicosanoids by LC-MS/MS Reveals Alterations in the Metabolic Profile after Smoking Cessation.
    Chem Res Toxicol 2018 Feb 13. Epub 2018 Feb 13.
    ABF, Analytisch-Biologisches Forschungslabor GmbH , Semmelweisstraße 5, 82152 Planegg, Germany.
    A preceding untargeted metabolic fingerprinting approach in our lab followed by targeted fatty acid analysis revealed alterations in arachidonic acid metabolism in samples derived from a diet-controlled smoking cessation study in which compliant subjects (N = 39) quit smoking at baseline and were followed over the course of 3 months. Consequently, urinary eicosanoids were evaluated by means of a validated LC-MS/MS method. A significant decrease was obtained for the prostaglandins PGF, 8-iso-PGF, thromboxane 2,3-d-TXB, and leukotriene Eupon quitting smoking. Read More

    Product Studies and Mechanistic Analysis of the Reaction of Methylglyoxal with Deoxyguanosine.
    Chem Res Toxicol 2018 Feb 31;31(2):105-115. Epub 2018 Jan 31.
    Department of Molecular Medicine, City of Hope and Beckman Research Institute , Duarte, California 91010, United States.
    Methylglyoxal (MG) is a highly reactive electrophile produced endogenously as a byproduct of glucose metabolism and protein catabolism and exogenously as a food contaminant. MG reacts spontaneously with proteins, lipids, and nucleic acids to form advanced glycation end products (AGEs), modifying or inhibiting their function. Protein AGEs are associated with pathological complications of diabetes, cancer, and neurodegenerative diseases, while the physiological impact of DNA, RNA, and lipid AGE formation is less well explored. Read More

    Computationally Assessing the Bioactivation of Drugs by N-Dealkylation.
    Chem Res Toxicol 2018 Feb 6;31(2):68-80. Epub 2018 Feb 6.
    Department of Pathology and Immunology, Washington University School of Medicine , Campus Box 8118, 660 S. Euclid Ave., St. Louis, Missouri 63110, United States.
    Cytochromes P450 (CYPs) oxidize alkylated amines commonly found in drugs and other biologically active molecules, cleaving them into an amine and an aldehyde. Metabolic studies usually neglect to report or investigate aldehydes, even though they can be toxic. It is assumed that they are efficiently detoxified into carboxylic acids and alcohols. Read More

    α,β-Unsaturated Aldehyde-Induced Delays in Nucleotide Excision Repair and the Contribution of Reactive Oxygen Species.
    Chem Res Toxicol 2018 Feb 17;31(2):145-155. Epub 2018 Jan 17.
    Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka , 52-1 Yada, Shizuoka 422-8526, Japan.
    Aldehydes are widespread environmental and industrial compounds to which humans are frequently exposed. Despite their significant health risk, the mechanisms underlying aldehyde toxicity are poorly understand. We recently demonstrated that cigarette sidestream smoke (CSS) inhibited nucleotide excision repair (NER), and this was attributed to aldehydes in CSS. Read More

    Reduction and Scavenging of Chemically Reactive Drug Metabolites by NAD(P)H:Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 and Variability in Hepatic Concentrations.
    Chem Res Toxicol 2018 Feb 11;31(2):116-126. Epub 2018 Jan 11.
    AIMMS-Division of Molecular Toxicology, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit , De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.
    Detoxicating enzymes NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) catalyze the two-electron reduction of quinone-like compounds. The protective role of the polymorphic NQO1 and NQO2 enzymes is especially of interest in the liver as the major site of drug bioactivation to chemically reactive drug metabolites. In the current study, we quantified the concentrations of NQO1 and NQO2 in 20 human liver donors and NQO1 and NQO2 activities with quinone-like drug metabolites. Read More

    Structural Identification and Kinetic Analysis of the in Vitro Products Formed by Reaction of Bisphenol A-3,4-quinone with N-Acetylcysteine and Glutathione.
    Chem Res Toxicol 2018 Feb 16;31(2):81-87. Epub 2018 Jan 16.
    Department of Chemistry, University of Nebraska at Omaha , 6001 Dodge Street, Durham Science Center, Omaha, Nebraska 68182, United States.
    Bisphenol A (BPA) has received considerable attention as an endocrine disrupting chemical and a possible substrate for genotoxic metabolites. BPA metabolism leads to formation of electrophilic o-quinones cable of binding to DNA and other endogenous nucleophiles. We have structurally identified the products resulting from the reaction of bisphenol A-3,4-quinone (BPAQ) with N-acetylcysteine (NAC) and glutathione (GSH). Read More

    Nucleic Bases Alkylation with Acrylonitrile and Cyanoethylene Oxide: A Computational Study.
    Chem Res Toxicol 2018 Feb 12;31(2):97-104. Epub 2018 Jan 12.
    Faculty of Chemistry and Chemical Technology, University of Maribor , Smetanova 17, SI-2000 Maribor, Slovenia.
    Acrylonitrile (AN) is widely used in the manufacture of resins, plastics, and polymers, where workers are exposed to it during its production, transportation, and application. After intake a portion of AN is converted to cyanoethylene oxide (CEO) by cytochrome P450 2E1. Both AN and CEO represent possible chemical carcinogens leading to DNA damage mainly in the form of the major 7-(2-oxoethyl)deoxyguanosine adduct. Read More

    HU-331 and Oxidized Cannabidiol Act as Inhibitors of Human Topoisomerase IIα and β.
    Chem Res Toxicol 2018 Feb 8;31(2):137-144. Epub 2018 Jan 8.
    Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Lipscomb University , Nashville, Tennessee 37204-3951, United States.
    Topoisomerase II is a critical enzyme in replication, transcription, and the regulation of chromatin topology. Several anticancer agents target topoisomerases in order to disrupt cell growth. Cannabidiol is a major non-euphoriant, pharmacologically active component of cannabis. Read More

    Dose and Diet - Sources of Arsenic Intake in Mouse in Utero Exposure Scenarios.
    Chem Res Toxicol 2018 Feb 2;31(2):156-164. Epub 2018 Jan 2.
    Institute of Chemistry, NAWI Graz, University of Graz , 8010 Graz, Austria.
    In humans, early life exposure to inorganic arsenic is associated with adverse health effects. Inorganic arsenic in utero or in early postnatal life also produces adverse health effects in offspring of pregnant mice that consumed drinking water containing low part per billion levels of inorganic arsenic. Because aggregate exposure of pregnant mice to inorganic arsenic from both drinking water and food has not been fully evaluated in experimental studies, quantifying arsenic exposure of the developing mouse is problematic. Read More

    Curcumin Derivative Epigenetically Reactivates Nrf2 Antioxidative Stress Signaling in Mouse Prostate Cancer TRAMP C1 Cells.
    Chem Res Toxicol 2018 Feb 8;31(2):88-96. Epub 2018 Jan 8.
    Department of Bioscience Technology, Chung Yuan Christian University , 200 Chung Pei Road, Chung Li District, Taoyuan City, Taiwan 32023, R.O.C.
    The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-bis-(3,4,5-trimethoxybenzylidene)-tetrahydro-thiopyran-4-one (F10) and (3E,5E)-3,5-bis-(3,4,5-trimethoxy-benzylidene)-tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin, and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways. Read More

    Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation.
    Chem Res Toxicol 2018 Jan 14;31(1):37-47. Epub 2017 Dec 14.
    Departments of Chemistry and Toxicology, University of Guelph , Guelph, Ontario N1G 2W1, Canada.
    Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. The most studied C8-dG adducts are formed from arylamines and contain a N-linkage separating the dG from the C8-aryl moiety. Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. Read More

    Bonding of Butylparaben, Bis(2-ethylhexyl)-phthalate, and Perfluorooctanesulfonic Acid to DNA: Comparison with Benzo[a]pyrene Shows Low Probability for Strong Noncovalent DNA Intercalation.
    Chem Res Toxicol 2018 Jan 29;31(1):22-36. Epub 2017 Nov 29.
    Department of Cellular and Molecular Biology, Computational Ecotoxicity Group, Uppsala University , Husargatan 3, SE-75124 Uppsala, Sweden.
    Parabens, phthalates, and perfluorinated compounds are pollutant compounds used in cosmetics, plastics, and fire-fighting foams. All three compounds have been studied over several years for toxicity mechanism; however, a clear view of their ability to bind to DNA has not been supplied empirically. In this work, a simulation study is done to reveal the interaction of three of these pollutants, bis(2-ethylhexyl)-phthalate (DEHP), butylparaben (BPRB), and the protonated form of perfluorooctanesulfonic acid (PFOS(H)), with DNA. Read More

    Bypass of an Abasic Site via the A-Rule by DNA Polymerase of Pseudomonas aeruginosa Phage PaP1.
    Chem Res Toxicol 2018 Jan 11;31(1):58-65. Epub 2017 Dec 11.
    Public Health Laboratory Sciences and Toxicology, West China School of Public Health, Sichuan University , Chengdu 610041, China.
    The abasic site is one the most common DNA lesions formed in cells; it induces a severe blockage of DNA replication and is highly mutagenic. We continue to use Gp90 exo, the sole DNA polymerase from Pseudomonas aeruginosa phage PaP1, to study DNA replication upon encountering an abasic site lesion. Gp90 exocan incorporate dNTPs opposite the abasic site, but extension past this site is extremely slow. Read More

    Effects of Solvent and Temperature on Free Radical Formation in Electronic Cigarette Aerosols.
    Chem Res Toxicol 2018 Jan 8;31(1):4-12. Epub 2017 Dec 8.
    Department of Public Health Sciences, Pennsylvania State University Tobacco Center of Regulatory Science (TCORS), Pennsylvania State University College of Medicine , Hershey, Pennsylvania 17033, United States.
    The ever-evolving market of electronic cigarettes (e-cigarettes) presents a challenge for analyzing and characterizing the harmful products they can produce. Earlier we reported that e-cigarette aerosols can deliver high levels of reactive free radicals; however, there are few data characterizing the production of these potentially harmful oxidants. Thus, we have performed a detailed analysis of the different parameters affecting the production of free radical by e-cigarettes. Read More

    The Toxmatrix: Chemo-Genomic Profiling Identifies Interactions That Reveal Mechanisms of Toxicity.
    Chem Res Toxicol 2018 Feb 4;31(2):127-136. Epub 2017 Dec 4.
    National Center for Advancing Translational Sciences (NCATS), National Institutes of Health , 9800 Medical Center Drive, Bethesda, Maryland 20892, United States.
    A chemical genomics "Toxmatrix" method was developed to elucidate mechanisms of cytotoxicity using neuronal models. Quantitative high-throughput screening (qHTS) was applied to systematically screen each toxicant against a panel of 70 modulators, drugs or chemicals that act on a known target, to identify interactions that either protect or sensitize cells to each toxicant. Thirty-two toxicants were tested at 10 concentrations for cytotoxicity to SH-SY5Y human neuroblastoma cells, with results fitted to the Hill equation to determine an ICfor each toxicant. Read More

    Chronic Arsenic Exposure Increases AβProduction and Receptor for Advanced Glycation End Products Expression in Rat Brain.
    Chem Res Toxicol 2018 Jan 4;31(1):13-21. Epub 2017 Dec 4.
    Laboratorio Nacional Forense Nuclear, Instituto Nacional de Investigaciones Nucleares , Carretera México-Toluca s/n, CP 52750 La Marquesa Ocoyoacac, México.
    Chronic arsenic exposure during development is associated with alterations of chemical transmission and demyelination, which result in cognitive deficits and peripheral neuropathies. At the cellular level, arsenic toxicity involves increased generation of reactive species that induce severe cellular alterations such as DNA fragmentation, apoptosis, and lipid peroxidation. It has been proposed that arsenic-associated neurodegeneration could evolve to Alzheimer disease in later life. Read More

    Assessment of Antipiperacillin IgG Binding to Structurally Related Drug Protein Adducts.
    Chem Res Toxicol 2017 Dec 22;30(12):2097-2099. Epub 2017 Nov 22.
    Department of Pharmacology, University of Liverpool , Sherrington Building, Ashton Street, Liverpool L69 3GE, England.
    The risk of developing hypersensitivity to alternative antibiotics is a concern for penicillin hypersensitive patients and healthcare providers. Herein we use piperacillin hypersensitivity as a model to explore the reactivity of drug-specific IgG against alternative β-lactam protein adducts. Mass spectrometry was used to show the drugs (amoxicillin, flucloxacillin, benzyl penicillin, aztreonam, and piperacillin) bind to similar lysine residues on the protein carrier bovine serum albumin. Read More

    Monoclonal Antibody That Recognizes Diethoxyphosphotyrosine-Modified Proteins and Peptides Independent of Surrounding Amino Acids.
    Chem Res Toxicol 2017 Dec 28;30(12):2218-2228. Epub 2017 Nov 28.
    Eppley Institute, University of Nebraska Medical Center , Omaha, Nebraska 68198, United States.
    Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are irreversibly inhibited by organophosphorus pesticides through formation of a covalent bond with the active site serine. Proteins that have no active site serine, for example albumin, are covalently modified on tyrosine and lysine. Chronic illness from pesticide exposure is not explained by inhibition of AChE and BChE. Read More

    Methyl DNA Phosphate Adduct Formation in Rats Treated Chronically with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol.
    Chem Res Toxicol 2018 Jan 30;31(1):48-57. Epub 2017 Nov 30.
    Masonic Cancer Center, University of Minnesota , 2231 Sixth Street SE, 2-152 CCRB, Minneapolis, Minnesota 55455, United States.
    The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a powerful lung carcinogen in animal models and is considered a causative factor for lung cancer in tobacco users. NNK is stereoselectively and reversibly metabolized to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is also a lung carcinogen. Both NNK and NNAL undergo metabolic activation by α-hydroxylation on their methyl groups to form pyridyloxobutyl and pyridylhydroxybutyl DNA base and phosphate adducts, respectively. Read More

    Molecular Signatures Associated with Treatment of Triple-Negative MDA-MB231 Breast Cancer Cells with Histone Deacetylase Inhibitors JAHA and SAHA.
    Chem Res Toxicol 2017 Dec 12;30(12):2187-2196. Epub 2017 Nov 12.
    Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo , Viale delle Scienze, 90128 Palermo, Italy.
    Jay Amin hydroxamic acid (JAHA; N8-ferrocenylN-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 an ICof 8.45 μM. Read More

    A Rapid Throughput Method To Extract DNA from Formalin-Fixed Paraffin-Embedded Tissues for Biomonitoring Carcinogenic DNA Adducts.
    Chem Res Toxicol 2017 Dec 27;30(12):2130-2139. Epub 2017 Nov 27.
    Masonic Cancer Center, Division of Carcinogenesis and Chemoprevention and Department of Medicinal Chemistry, ‡Department of Laboratory Medicine and Pathology, and §Department of Urology, University of Minnesota , Minneapolis, Minnesota 55455, United States.
    Formalin-fixed paraffin-embedded (FFPE) tissues are rarely used for screening DNA adducts of carcinogens because the harsh conditions required to reverse the formaldehyde-mediated DNA cross-links can destroy DNA adducts. We recently adapted a commercial silica-based column kit used in genomics to manually isolate DNA under mild conditions from FFPE tissues of rodents and humans and successfully measured DNA adducts of several carcinogens including aristolochic acid I (AA-I), 4-aminobiphenyl (4-ABP), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (Yun et al. (2013) Anal. Read More

    Relative Propensities of Cytochrome c Oxidase and Cobalt Corrins for Reaction with Cyanide and Oxygen: Implications for Amelioration of Cyanide Toxicity.
    Chem Res Toxicol 2017 Dec 21;30(12):2197-2208. Epub 2017 Nov 21.
    Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States.
    In aqueous media at neutral pH, the binding of two cyanide molecules per cobinamide can be described by two formation constants, K= 1.1 (±0.6) × 10Mand K= 8. Read More

    The Capture of Cadmium by Reactive Polysulfides Attenuates Cadmium-Induced Adaptive Responses and Hepatotoxicity.
    Chem Res Toxicol 2017 Dec 20;30(12):2209-2217. Epub 2017 Nov 20.
    Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
    Cadmium (Cd) is an environmental electrophile that modifies protein nucleophiles, thereby modulating cellular signaling and toxicity. While reactive persulfides/polysulfides exhibit relatively high nucleophilic properties, their roles in the altered gene expression and toxicity caused by Cd remain unclear. Exposing primary mouse hepatocytes to Cd caused heat shock protein 70 (HSP70) and metallothionein (MT)-I/II to be upregulated and cytotoxicity to occur. Read More

    Early Metabolome Profiling and Prognostic Value in Paraquat-Poisoned Patients: Based on Ultraperformance Liquid Chromatography Coupled To Quadrupole Time-of-Flight Mass Spectrometry.
    Chem Res Toxicol 2017 Dec 13;30(12):2151-2158. Epub 2017 Nov 13.
    Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000, China.
    Paraquat (PQ) has caused countless deaths throughout the world. There remains no effective treatment for PQ poisoning. Here we study the blood metabolome of PQ-poisoned patients using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). Read More

    Refinement of a Methodology for Untargeted Detection of Serum Albumin Adducts in Human Populations.
    Chem Res Toxicol 2017 Dec 17;30(12):2120-2129. Epub 2017 Nov 17.
    MRC-PHE Centre for Environment and Health, Department of Analytical, Environmental, and Forensic Sciences, Faculty of Life Sciences and Medicine, King's College London , Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom.
    Covalently modified blood proteins (e.g., serum albumin adducts) are increasingly being viewed as potential biomarkers via which the environmental causes of human diseases may be understood. Read More

    Sulfide Toxicity and Its Modulation by Nitric Oxide in Bovine Pulmonary Artery Endothelial Cells.
    Chem Res Toxicol 2017 Dec 10;30(12):2100-2109. Epub 2017 Nov 10.
    Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh , 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
    Bovine pulmonary artery endothelial cells (BPAEC) respond in a dose-dependent manner to millimolar (0-10) levels of sodium sulfide (NaHS). No measurable increase in caspase-3 activity and no change in the extent of autophagy (or mitophagy) were observed in BPAEC. However, lactate dehydrogenase levels increased in the BPAEC exposed NaHS, which indicated necrotic cell death. Read More

    Effects of Black Raspberry Extract and Berry Compounds on Repair of DNA Damage and Mutagenesis Induced by Chemical and Physical Agents in Human Oral Leukoplakia and Rat Oral Fibroblasts.
    Chem Res Toxicol 2017 Dec 15;30(12):2159-2164. Epub 2017 Nov 15.
    Department of Medicine, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
    Black raspberries (BRB) have been shown to inhibit carcinogenesis in a number of systems, with most studies focusing on progression. Previously we reported that an anthocyanin-enriched black raspberry extract (BE) enhanced repair of dibenzo-[a,l]-pyrene dihydrodiol (DBP-diol)-induced DNA adducts and inhibited DBP-diol and DBP-diolepoxide (DBPDE)-induced mutagenesis in a lacI rat oral fibroblast cell line, suggesting a role for BRB in the inhibition of initiation of carcinogenesis. Here we extend this work to protection by BE against DNA adduct formation induced by dibenzo-[a,l]-pyrene (DBP) in a human oral leukoplakia cell line (MSK) and to a second carcinogen, UV light. Read More

    Age-Dependent Effects of Acute Alcohol Administration in the Hippocampal Phosphoproteome.
    Chem Res Toxicol 2017 Dec 3;30(12):2165-2173. Epub 2017 Nov 3.
    Laboratorio de Farmacología, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia. Universidad CEU-San Pablo , 28668 Madrid, Spain.
    Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. Read More

    Active Site Interactions Impact Phosphoryl Transfer during Replication of Damaged and Undamaged DNA by Escherichia coli DNA Polymerase I.
    Chem Res Toxicol 2017 Nov 25;30(11):2033-2043. Epub 2017 Oct 25.
    Department of Biochemistry and Molecular Biology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine , Hershey, Pennsylvania 17033, United States.
    Replicative DNA polymerases are able to discriminate between very similar substrates with high accuracy. One mechanism by which E. coli DNA polymerase I checks for Watson-Crick geometry is through a hydrogen bonding fork between Arg668 and the incoming dNTP and the minor groove of the primer terminus. Read More

    Dapsone and Nitroso Dapsone Activation of Naı̈ve T-Cells from Healthy Donors.
    Chem Res Toxicol 2017 Dec 31;30(12):2174-2186. Epub 2017 Oct 31.
    MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool , Liverpool L69 3GE, United Kingdom.
    Dapsone (DDS) causes hypersensitivity reactions in 0.5-3.6% of patients. Read More

    Potential Metabolic Activation of Representative Alkylated Polycyclic Aromatic Hydrocarbons 1-Methylphenanthrene and 9-Ethylphenanthrene Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells.
    Chem Res Toxicol 2017 Dec 27;30(12):2140-2150. Epub 2017 Oct 27.
    Synthetic Organic Chemistry Core, Center in Environmental Toxicology, University of Texas Medical Branch at Galveston , Galveston, Texas 77555-1110, United States.
    Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. Alkylated phenanthrenes are the most abundant PPAHs present in the crude oil and could contaminate the food chain. We describe the metabolism of a C-phenanthrene regioisomer 1-methylphenanthrene (1-MP) and a C-phenanthrene regioisomer 9-ethylphenanthrene (9-EP) in human HepG2 cells. Read More

    Nicotine Alters the Gut Microbiome and Metabolites of Gut-Brain Interactions in a Sex-Specific Manner.
    Chem Res Toxicol 2017 Dec 16;30(12):2110-2119. Epub 2017 Nov 16.
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
    As the primary active substance in tobacco, nicotine affects the activity of the central nervous system, and its effects are sex-dependent. There are complex interactions between the gut and brain, and the gut microbiome can influence neuronal activity and host behavior, with diverse chemical signaling being involved. However, it is unclear whether nicotine can affect the normal gut microbiome and associated chemical signaling of the gut-brain axis. Read More

    Influence of DNA Lesions on Polymerase-Mediated DNA Replication at Single-Molecule Resolution.
    Chem Res Toxicol 2017 Nov 23;30(11):1972-1983. Epub 2017 Oct 23.
    Molecular Virology, Department of Medicine, Imperial College London , Du Cane Road, London W12 0NN, U.K.
    Faithful replication of DNA is a critical aspect in maintaining genome integrity. DNA polymerases are responsible for replicating DNA, and high-fidelity polymerases do this rapidly and at low error rates. Upon exposure to exogenous or endogenous substances, DNA can become damaged and this can alter the speed and fidelity of a DNA polymerase. Read More

    Red Clover Aryl Hydrocarbon Receptor (AhR) and Estrogen Receptor (ER) Agonists Enhance Genotoxic Estrogen Metabolism.
    Chem Res Toxicol 2017 Nov 19;30(11):2084-2092. Epub 2017 Oct 19.
    UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , 833 S. Wood Street, Chicago, Illinois 60612-7231, United States.
    Many women consider botanical dietary supplements (BDSs) as safe alternatives to hormone therapy for menopausal symptoms. However, the effect of BDSs on breast cancer risk is largely unknown. In the estrogen chemical carcinogenesis pathway, P450 1B1 metabolizes estrogens to 4-hydroxylated catechols, which are oxidized to genotoxic quinones that initiate and promote breast cancer. Read More

    Mechanism of Error-Free DNA Replication Past Lucidin-Derived DNA Damage by Human DNA Polymerase κ.
    Chem Res Toxicol 2017 Nov 23;30(11):2023-2032. Epub 2017 Oct 23.
    Department of Chemistry, Indian Institute of Technology Bombay , Mumbai 400076, India.
    DNA damage impinges on genetic information flow and has significant implications in human disease and aging. Lucidin-3-O-primeveroside (LuP) is an anthraquinone derivative present in madder root, which has been used as a coloring agent and food additive. LuP can be metabolically converted to genotoxic compound lucidin, which subsequently forms lucidin-specific N-2'-deoxyguanosine (N-dG) and N-2'-deoxyadenosine (N-dA) DNA adducts. Read More

    Simultaneous Mass Spectrometric Analysis of Methylated and Ethylated Peptides in Human Hemoglobin: Correlation with Cigarette Smoking.
    Chem Res Toxicol 2017 Nov 12;30(11):2074-2083. Epub 2017 Oct 12.
    Department of Chemistry and Biochemistry, National Chung Cheng University , 168 University Road, Ming-Hsiung, Chia-Yi 62142, Taiwan.
    Alkylating agents contained in cigarettes smoke might be related to cancer development. Post-translational protein methylation and ethylation may cause alteration of protein functions. Human hemoglobin (Hb) has been a target for molecular dosimetry because of its easy accessibility. Read More

    A Chemoproteomic Platform To Assess Bioactivation Potential of Drugs.
    Chem Res Toxicol 2017 10 6;30(10):1797-1803. Epub 2017 Oct 6.
    State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine , Beijing 102206, China.
    Reactive metabolites (RM) formed from bioactivation of drugs can covalently modify liver proteins and cause mechanism-based inactivation of major cytochrome P450 (CYP450) enzymes. Risk of bioactivation of a test compound is routinely examined as part of lead optimization efforts in drug discovery. Here we described a chemoproteomic platform to assess in vitro and in vivo bioactivation potential of drugs. Read More

    Synthesis, Characterization, and Identification of New in Vitro Covalent DNA Adducts of Divinyl Sulfone, an Oxidative Metabolite of Sulfur Mustard.
    Chem Res Toxicol 2017 10 5;30(10):1874-1882. Epub 2017 Oct 5.
    State Key Laboratory of Toxicology and Medical Countermeasures and Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences , 27 Taiping Road, Haidian District, Beijing 100850, China.
    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 this paper was to identify whether DVS could covalently bind to DNA bases to form new DNA adducts in cells in vitro. Read More

    Biotransformation of Isoniazid by Cytochromes P450: Analyzing the Molecular Mechanism using Density Functional Theory.
    Chem Res Toxicol 2017 Nov 16;30(11):2060-2073. Epub 2017 Oct 16.
    Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) , Sector -67, S. A. S. Nagar, Mohali, 160 062 Punjab, India.
    Hydrazide group (-C(O)-NH-NH) is considered as a structural alert in the drug discovery process because the biotransformation chemistry of this group leads to the generation of toxic radical intermediates. The most important antitubercular drug isoniazid (INH) carries the hydrazide group. The toxicity of INH has been attributed to the protein adduct formation involving isonicotinoyl radical. Read More

    "Juice Monsters": Sub-Ohm Vaping and Toxic Volatile Aldehyde Emissions.
    Chem Res Toxicol 2017 10 29;30(10):1791-1793. Epub 2017 Sep 29.
    Mechanical Engineering Department, Faculty of Engineering and Architecture, American University of Beirut , Bliss Street, P.O. Box 11-0236, Beirut, Lebanon.
    An emerging category of electronic cigarettes (ECIGs) is sub-Ohm devices (SODs) that operate at ten or more times the power of conventional ECIGs. Because carcinogenic volatile aldehyde (VA) emissions increase sharply with power, SODs may expose users to greater VAs. In this study, we compared VA emissions from several SODs and found that across device, VAs and power were uncorrelated unless power was normalized by coil surface area. Read More

    Detoxification of Atrazine by Low Molecular Weight Thiols in Alfalfa (Medicago sativa).
    Chem Res Toxicol 2017 10 4;30(10):1835-1846. Epub 2017 Oct 4.
    Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University , Nanjing 210095, China.
    Low molecular weight (LMW) thiols in higher plants are a group of sulfur-rich nonprotein compounds and play primary and multiple roles in cellular redox homeostasis, enzyme activities, and xenobiotics detoxification. This study focused on identifying thiols-related protein genes from the legume alfalfa exposed to the herbicide atrazine (ATZ) residues in environment. Using high-throughput RNA-sequencing, a set of ATZ-responsive thiols-related protein genes highly up-regulated and differentially expressed in alfalfa was identified. Read More

    Hemoglobin Adducts and Urinary Metabolites of Arylamines and Nitroarenes.
    Chem Res Toxicol 2017 10 21;30(10):1733-1766. Epub 2017 Sep 21.
    Institute of Environmental and Occupational Toxicology , Casella Postale 108, CH-6780 Airolo, Switzerland.
    Arylamines and nitroarenes are intermediates in the production of pharmaceuticals, dyes, pesticides, and plastics and are important environmental and occupational pollutants. N-Hydroxyarylamines are the toxic common intermediates of arylamines and nitroarenes. N-Hydroxyarylamines and their derivatives can form adducts with hemoglobin (Hb-adducts), albumin, DNA, and tissue proteins in a dose-dependent manner. Read More

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