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    5414 results match your criteria Chemical Research in Toxicology [Journal]

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    Solvent and Temperature Effects on Free Radical Formation in Electronic Cigarette Aerosols.
    Chem Res Toxicol 2017 Nov 21. Epub 2017 Nov 21.
    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 is little data characterizing the production of these potentially harmful oxidants. Thus, we have performed a detailed analysis of the different parameters affecting free radical production from e-cigarettes. Read More

    The Toxmatrix: Chemo-genomic profiling identifies interactions that reveal mechanisms of toxicity.
    Chem Res Toxicol 2017 Nov 20. Epub 2017 Nov 20.
    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 IC50 for each toxicant. Read More

    Chronic arsenic exposure increases Aβ(1-42) production and RAGE expression in rat brain.
    Chem Res Toxicol 2017 Nov 20. Epub 2017 Nov 20.
    Chronic arsenic exposure during development is associated with alterations of chemical transmission and demyelination, which result in cognitive deficits and peripheral neuropathies. At 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 Nov 22. 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 diethoxyphospho-tyrosine modified proteins and peptides independent of surrounding amino acids.
    Chem Res Toxicol 2017 Nov 14. Epub 2017 Nov 14.
    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 2017 Nov 13. Epub 2017 Nov 13.
    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 Nov 12. 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(1)-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 IC50 of 8.45 μM. Read More

    A Rapid Throughput Method to Extract DNA from Formalin-Fixed Paraffin-Embedded Tissues for Biomonitoring Carcinogenic DNA Adducts in Humans.
    Chem Res Toxicol 2017 Nov 9. Epub 2017 Nov 9.
    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 Nov 21. 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, Kf1 = 1.1 (±0.6) × 10(5) M(-1) and Kf2 = 8. Read More

    The Capture of Cadmium by Reactive Polysulfides Attenuates Cadmium-Induced Adaptive Responses and Hepatotoxicity.
    Chem Res Toxicol 2017 Nov 20. 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 Nov 13. 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 Nov 17. 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 Nov 10. 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 Nov 15. 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 Nov 3. 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 Oct 31. 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 Oct 27. 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 C1-phenanthrene regioisomer 1-methylphenanthrene (1-MP) and a C2-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 Nov 16. 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)-2'-deoxyguanosine (N(2)-dG) and N(6)-2'-deoxyadenosine (N(6)-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 Oct 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 Oct 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-NH2) 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 Oct 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 Oct 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 Oct 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

    Potential of Phenylbutyrate as Adjuvant Chemotherapy: An Overview of Cellular and Molecular Anticancer Mechanisms.
    Chem Res Toxicol 2017 Oct 3;30(10):1767-1777. Epub 2017 Oct 3.
    Jordan University of Science and Technology , College of Pharmacy, Department of Clinical Pharmacy, P.O. Box 3030, Irbid 22110, Jordan.
    Despite the advancement in cancer therapy, a high number of patients fail treatment because of drug resistance. Several preclinical in vitro data suggest that phenylbutyrate has antiproliferative, antiangiogenic, antimetastatic, immunomodulatory, and differentiating properties. Moreover, phenylbutyrate administration in vivo provided an oncoprotective effect. Read More

    Benchmark Dose Modeling Estimates of the Concentrations of Inorganic Arsenic That Induce Changes to the Neonatal Transcriptome, Proteome, and Epigenome in a Pregnancy Cohort.
    Chem Res Toxicol 2017 Oct 27;30(10):1911-1920. Epub 2017 Sep 27.
    Department of Environmental Sciences and Engineering, The University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27516, United States.
    Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling. Read More

    Copper Inhibits the AlkB Family DNA Repair Enzymes under Wilson's Disease Condition.
    Chem Res Toxicol 2017 Oct 26;30(10):1794-1796. Epub 2017 Sep 26.
    Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island , Kingston, Rhode Island 02881, United States.
    Disturbed metabolism of copper ions can cause diseases such as Wilson's disease (WD). In this work, we investigated the inhibitory effect of Cu(II) ion in vitro on the AlkB family DNA repair enzymes, which are members of the Fe(II)/alpha-ketoglutarate-dependent dioxygenase and include human ALKBH2, ALKBH3, and E. coli AlkB proteins. Read More

    Dose-Dependent Response to 3-Nitrobenzanthrone Exposure in Human Urothelial Cancer Cells.
    Chem Res Toxicol 2017 Oct 28;30(10):1855-1864. Epub 2017 Sep 28.
    Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg , Schillerstr. 25/29, 91054 Erlangen, Germany.
    A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterize the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0. Read More

    Investigation of Dioscorea bulbifera Rhizome-Induced Hepatotoxicity in Rats by a Multisample Integrated Metabolomics Approach.
    Chem Res Toxicol 2017 Oct 22;30(10):1865-1873. Epub 2017 Sep 22.
    State Key Laboratory of Natural Medicines, China Pharmaceutical University , No. 24 Tongjia Lane, Nanjing 210009, China.
    The use of herbal medicines continues to expand globally, meanwhile, herb-associated hepatotoxicity is becoming a safety issue. As a conventional Chinese medicinal herb, Dioscorea bulbifera rhizome (DBR) has been documented to cause hepatic toxicity. However, the exact underlying mechanism remains largely unexplored. Read More

    Transcriptomic Analysis of Thalidomide Challenged Chick Embryo Suggests Possible Link between Impaired Vasculogenesis and Defective Organogenesis.
    Chem Res Toxicol 2017 Oct 27;30(10):1883-1896. Epub 2017 Sep 27.
    SciGenom Laboratories, Cochin, Kerala 682037, India.
    Since the conception of thalidomide as a teratogen, approximately 30 hypotheses have been put forward to explain the developmental toxicity of the molecule. However, no systems biology approach has been taken to understand the phenomena yet. The proposed work was aimed to explore the mechanism of thalidomide toxicity in developing chick embryo in the context of transcriptomics by using genome wide RNA sequencing data. Read More

    Immunopurification of Acetylcholinesterase from Red Blood Cells for Detection of Nerve Agent Exposure.
    Chem Res Toxicol 2017 Oct 25;30(10):1897-1910. Epub 2017 Sep 25.
    Eppley Institute, University of Nebraska Medical Center , Omaha, Nebraska 68198, United States.
    Nerve agents and organophosphorus pesticides make a covalent bond with the active site serine of acetylcholinesterase (AChE), resulting in inhibition of AChE activity and toxic symptoms. AChE in red blood cells (RBCs) serves as a surrogate for AChE in the nervous system. Mass spectrometry analysis of adducts on RBC AChE could provide evidence of exposure. Read More

    Multidrug Resistance Protein 4 (MRP4/ABCC4) Protects Cells from the Toxic Effects of Halobenzoquinones.
    Chem Res Toxicol 2017 Oct 22;30(10):1815-1822. Epub 2017 Sep 22.
    Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, Alberta, Canada T6G 2G3.
    Halobenzoquinones (HBQs) are frequently detected disinfection byproducts (DBPs) in treated water. Recent studies have demonstrated that HBQs are highly cytotoxic and capable of inducing the generation of reactive oxygen species (ROS) and depleting cellular glutathione (GSH). Multidrug resistance proteins (MRPs/ABCCs) are known to play a critical role in the elimination of numerous drugs, carcinogens, toxicants, and their conjugated metabolites. Read More

    A Multiplatform Approach for the Discovery of Novel Drug-Induced Kidney Injury Biomarkers.
    Chem Res Toxicol 2017 Oct 27;30(10):1823-1834. Epub 2017 Sep 27.
    Boehringer Ingelheim Pharmaceuticals , Ridgefield, Connecticut 06877, United States.
    Drug-induced kidney injury (DIKI) is a common toxicity observed in pharmaceutical development. We demonstrated the use of label-free liquid chromatography-mass spectrometry (LC-MS) and multiplex liquid chromatography-single reaction monitoring (LC-SRM) as practical extensions of standard immunoassay based safety biomarker assessments for identification of new toxicity marker candidates and for improved mechanistic understanding. Two different anticancer drugs, doxorubicin (DOX) and cisplatin (cis-diamminedichloridoplatinum, CDDP), were chosen as the toxicants due to their different modes of nephrotoxicity. Read More

    Coordination and Substitution of DNA Polymerases in Response to Genomic Obstacles.
    Chem Res Toxicol 2017 Nov 22;30(11):1956-1971. Epub 2017 Sep 22.
    Department of Chemistry and Biochemistry, Baylor University , Waco, Texas 76798, United States.
    The ability for DNA polymerases (Pols) to overcome a variety of obstacles in its path to maintain genomic stability during replication is a complex endeavor. It requires the coordination of multiple Pols with differing specificities through molecular control and access to the replisome. Although a number of contacts directly between Pols and accessory proteins have been identified, forming the basis of a variety of holoenzyme complexes, the dynamics of Pol active site substitutions remain uncharacterized. Read More

    Computational Simulations of DNA Polymerases: Detailed Insights on Structure/Function/Mechanism from Native Proteins to Cancer Variants.
    Chem Res Toxicol 2017 Nov 15;30(11):1922-1935. Epub 2017 Sep 15.
    Department of Chemistry, University of North Texas , 1155 Union Circle, Denton, Texas 76203, United States.
    Genetic information is vital in the cell cycle of DNA-based organisms. DNA polymerases (DNA Pols) are crucial players in transactions dealing with these processes. Therefore, the detailed understanding of the structure, function, and mechanism of these proteins has been the focus of significant effort. Read More

    New Insights into DNA Polymerase Function Revealed by Phosphonoacetic Acid-Sensitive T4 DNA Polymerases.
    Chem Res Toxicol 2017 Nov 15;30(11):1984-1992. Epub 2017 Sep 15.
    Marine Science & Technology Institute Department of Environmental Science and Engineering, Yangzhou University , No. 196 Huayang West Road, Hanjiang, Yangzhou, Jiangsu 225127, China.
    The bacteriophage T4 DNA polymerase (pol) and the closely related RB69 DNA pol have been developed into model enzymes to study family B DNA pols. While all family B DNA pols have similar structures and share conserved protein motifs, the molecular mechanism underlying natural drug resistance of nonherpes family B DNA pols and drug sensitivity of herpes DNA pols remains unknown. In the present study, we constructed T4 phages containing G466S, Y460F, G466S/Y460F, P469S, and V475W mutations in DNA pol. Read More

    Structures of a DNA Polymerase Inserting Therapeutic Nucleotide Analogues.
    Chem Res Toxicol 2017 Nov 1;30(11):1993-2001. Epub 2017 Sep 1.
    Department of Biochemistry and Molecular Biology, University of Kansas Medical Center , Kansas City, Kansas 66160, United States.
    Members of the nucleoside analogue class of cancer therapeutics compete with canonical nucleotides to disrupt numerous cellular processes, including nucleotide homeostasis, DNA and RNA synthesis, and nucleotide metabolism. Nucleoside analogues are triphosphorylated and subsequently inserted into genomic DNA, contributing to the efficacy of therapeutic nucleosides in multiple ways. In some cases, the altered base acts as a mutagen, altering the DNA sequence to promote cellular death; in others, insertion of the altered nucleotide triggers DNA repair pathways, which produce lethal levels of cytotoxic intermediates such as single and double stranded DNA breaks. Read More

    Occupational Respiratory Exposure to Platinum Group Metals: A Review and Recommendations.
    Chem Res Toxicol 2017 Oct 15;30(10):1778-1790. Epub 2017 Sep 15.
    Occupational Hygiene and Health Research Initiative (OHHRI), North-West University , Potchefstroom 2520, South Africa.
    Platinum group metals (PGMs) is a group of metals that include platinum, palladium, rhodium, ruthenium, iridium, and osmium. Occupational respiratory exposure to platinum has been reported since 1945, but studies investigating occupational exposure to palladium, rhodium, ruthenium, iridium, and osmium are scarce. This review provides a summation of the information available on the respiratory exposure to PGMs in various industrial settings, methods used to assess exposure, and the possible adverse health effects resulting from occupational exposure to PGMs. Read More

    Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes.
    Chem Res Toxicol 2017 Oct 13;30(10):1847-1854. Epub 2017 Sep 13.
    Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University , P.O. Box 616, Maastricht 6200 MD, The Netherlands.
    Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis through mitochondrial dysfunction. The aim of this study is to further investigate VPA-induced mechanisms of steatosis by analyzing changes in patterns of methylation in nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Read More

    Biological Monitoring of Inhaled Nanoparticles in Patients: An Appealing Approach To Study Causal Link between Human Respiratory Pathology and Exposure to Nanoparticles.
    Chem Res Toxicol 2017 Sep 8;30(9):1655-1660. Epub 2017 Sep 8.
    Ecole Nationale Supérieure des Mines de Saint-Etienne, CIS-EMSE, SAINBIOSE, F-42023 Saint Etienne, France.
    Although necessary, in vitro and in vivo studies are not fully successful at predicting nanomaterials toxicity. We propose to associate such assays to the biological monitoring of nanoparticles in clinical samples to get more relevant data on the chemical and physical nature and dose of nanoparticles found in humans. The concept is to establish the load of nanoparticles in biological samples of patients. Read More

    Translesion DNA Synthesis in Cancer: Molecular Mechanisms and Therapeutic Opportunities.
    Chem Res Toxicol 2017 Nov 28;30(11):1942-1955. Epub 2017 Sep 28.
    Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205-7199, United States.
    The genomic landscape of cancer is one marred by instability, but the mechanisms that underlie these alterations are multifaceted and remain a topic of intense research. Cellular responses to DNA damage and/or replication stress can affect genome stability in tumors and influence the response of patients to therapy. In addition to direct repair, DNA damage tolerance (DDT) is an element of genomic maintenance programs that contributes to the etiology of several types of cancer. Read More

    Living on the Edge: DNA Polymerase Lambda between Genome Stability and Mutagenesis.
    Chem Res Toxicol 2017 Nov 8;30(11):1936-1941. Epub 2017 Sep 8.
    DNA Enzymology & Molecular Virology and Cell Nucleus & DNA replication Units, Institute of Molecular Genetics IGM-CNR , via Abbiategrasso 207, I-27100 Pavia, Italy.
    In human cells, only four DNA polymerases (pols) are necessary and sufficient for the duplication of the genetic information. However, more than a dozen DNA pols are required to maintain its integrity. Such a high degree of specialization makes DNA repair pols able to cope with specific lesions or repair pathways. Read More

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