5,657 results match your criteria Chemical Research in Toxicology [Journal]


Phenylarsine Oxide Can Induce Degradation of PLZF-RARα Variant Fusion Protein of Acute Promyelocytic Leukemia.

Chem Res Toxicol 2019 Mar 15. Epub 2019 Mar 15.

Inner Mongolia Medical University , Huhot , China.

PLZF-RARα is the second most frequent variant acute promyelocytic leukemia (APL) fusion protein that ranks after PML-RARα in APL. However, PLZF-RARα is resistant to current front line APL treatments including all transretinoic acid (ATRA), arsenic trioxide (ATO), and chemotherapy (i.e. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00072DOI Listing
March 2019
3.529 Impact Factor

Computational MitoTarget-Scanning Based on Topological Vacancies of Single-Walled Carbon Nanotubes with Human Mitochondrial hVDAC1 Channel.

Chem Res Toxicol 2019 Mar 14. Epub 2019 Mar 14.

We present an in-silico approach for modeling the non-covalent interactions between human mitochondrial voltage-dependent anion channel (hVDAC1) with a family of single walled carbon nanotubes (SWCNT) with a defined pattern of topological vacancies (from v = 1 to 16), obtained by removing atoms from the SWCNT surface. The general results showed more stable docking interaction complexes (SWCNT-hVDAC1), with more negative Gibbs free energy of binding-affinity values, and a strong dependence with the vacancy number (R2: 0.93) and vacancy formation energy (R2: 0. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00266DOI Listing

Integrated proteomics, biological functional assessments and metabolomics reveal toosendanin induced hepatic energy metabolic disorders.

Chem Res Toxicol 2019 Mar 8. Epub 2019 Mar 8.

Toosendanin (TSN), a compound from Melia toosendan, exerts severe hepatotoxicity, which restricts its clinical application. However, the mechanism is not clear. Our previous research found that covalent modification of TSN for proteins might be a possible reason using human liver microsome, and the glycolytic enzymes, triosephosphate isomerase 1 (TPIS) and α-enolase (ENOA), were responsible for the hepatotoxicity. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00350
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http://dx.doi.org/10.1021/acs.chemrestox.8b00350DOI Listing
March 2019
8 Reads

Mass Spectrometry Identifies Isopeptide Cross-Links Promoted by Diethylphosphorylated Lysine in Proteins Treated with Chlorpyrifos Oxon.

Chem Res Toxicol 2019 Mar 7. Epub 2019 Mar 7.

Eppley Institute , University of Nebraska Medical Center , Omaha , Nebraska 68198-5900 , United States.

Exposure to chlorpyrifos at doses that do not inhibit acetylcholinesterase can be followed by chronic illness in adults and developmental deficits in children. A mechanism to explain these effects is not available. Using mass spectrometry, we have found that chlorpyrifos oxon is a cross-linking agent. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00001DOI Listing

(de)Toxifying the Epigenetic Code.

Chem Res Toxicol 2019 Mar 6. Epub 2019 Mar 6.

Cells are continuously subjected to an array of reactive chemical species which are produced both endogenously through metabolic pathways and taken up exogenously by diet and exposure to drugs or toxins. As a result, proteins often undergo non-enzymatic covalent modifications (NECMs) by these chemically reactive/toxic species, which can alter protein structure, function, stability and binding partner affinity. NECMs accumulate over time and are linked to various diseases such as Alzheimer's disease, cancer and diabetes. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00013DOI Listing

Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity.

Chem Res Toxicol 2019 Mar 15. Epub 2019 Mar 15.

Thalidomide is an infamous teratogen and it is continuously being explored for its anticancer properties. Fibroblast growth factor receptors (FGFRs) are implicated in embryo development and cancer pathophysiology. With striking similarities observed between FGFR implicated conditions and thalidomide embryopathy, we hypothesized thalidomide targets FGFRs. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00286DOI Listing
March 2019
1 Read

Concentration-Dependent Dual Effects of Ciprofloxacin on SB-590885-Resistant BRAF A375 Melanoma Cells.

Chem Res Toxicol 2019 Mar 14. Epub 2019 Mar 14.

Department of Chemistry, Faculty of Science , Ferdowsi University of Mashhad , Mashhad , Iran.

BRAF inhibitors (BRAFi) have been applied to treat melanoma harboring V600E mutations. Several studies showed that BRAFi-resistant melanomas are dependent on mitochondrial biogenesis. Therefore, the present study aimed to investigate the influence of ciprofloxacin (CIP), a mitochondria-targeting antibiotic, on SB-590885-resistant BRAF A375 melanoma (A375/SB) cells. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00335DOI Listing

Oxidative Modification of Guanine in a Potential Z-DNA-Forming Sequence of a Gene Promoter Impacts Gene Expression.

Chem Res Toxicol 2019 Mar 7. Epub 2019 Mar 7.

Department of Chemistry , University of Utah , 315S 1400 East , Salt Lake City , Utah 84112-0850 , United States.

One response to oxidation of guanine (G) to 8-oxo-7,8-dihydroguanine (OG) in a gene promoter is regulation of mRNA expression suggesting an epigenetic-like role for OG. A proposed mechanism involves G oxidation within a potential G-quadruplex-forming sequence (PQS) in the promoter, enabling a structural shift from B-DNA to a G-quadruplex fold (G4). When OG was located in the coding vs template strand, base excision repair led to an on/off transcriptional switch. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00041DOI Listing
March 2019
2 Reads

Enzyme-Activated Generation of Reactive Oxygen Species from Heterocyclic N-Oxides under Aerobic and Anaerobic Conditions and Its Relevance to Hypoxia-Selective Prodrugs.

Chem Res Toxicol 2019 Mar 11. Epub 2019 Mar 11.

Enzymatic one-electron reduction of heterocyclic N-oxides can lead to the intracellular generation of reactive oxygen species via several different chemical pathways. These reactions may be relevant to hypoxia-selective anticancer drugs, antimicrobial agents, and unwanted toxicity of heterocylic nitrogen compounds. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00036DOI Listing
March 2019
1 Read

Idarubicin Stimulates Cell Cycle- and TET2-Dependent Oxidation of DNA 5-Methylcytosine in Cancer Cells.

Chem Res Toxicol 2019 Mar 11. Epub 2019 Mar 11.

State Key Laboratory of Environmental Chemistry and Ecotoxicoogy , Research Center for Eco-Environmental Sciences , Beijing 100085 , China.

The topoisomerase II inhibitor idarubicin (Ida) is an effective anticancer anthracycline drug and has been used for clinical therapies of multiple cancers. It is well-known that Ida and its analogues can induce DNA double strand breakage (DSB) by inhibiting topoisomer II and kill tumor cells. To date, it remains unknown whether they alter DNA epigenomes. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00012DOI Listing
March 2019
1 Read

Structural Foundation for Insect-Selective Activity of Acylpolyamine Toxins from Spider Araneus ventricosus.

Chem Res Toxicol 2019 Mar 6. Epub 2019 Mar 6.

College of Life Science and Environment , Hengyang Normal University , Hengyang 421002 , China.

Spider venoms are insecticidal mixtures with diverse biological activities, and acylpolyamines are their small molecular active components. However, the mechanism for the insecticidal activity of acylpolyamines remains to be elucidated. Here, the structure and function of two acylpolyamine toxins, AVTX-622 and AVTX-636, from Araneus ventricosus were investigated. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00337DOI Listing

Genotoxic and Epigenotoxic Alterations in the Lung and Liver of Mice Induced by Acrylamide: A 28 Day Drinking Water Study.

Chem Res Toxicol 2019 Mar 12. Epub 2019 Mar 12.

Division of Biochemical Toxicology , FDA National Center for Toxicological Research , Jefferson , Arkansas 72079 , United States.

Acrylamide has been classified as a "Group 2A carcinogen" (probably carcinogenic to humans) by the International Agency for Research on Cancer. The carcinogenicity of acrylamide is attributed to its well-recognized genotoxicity. In the present study, we investigated the effect of acrylamide on epigenetic alterations in mice. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00020DOI Listing
March 2019
1 Read

Metabolomics Analysis in Acute Paraquat Poisoning Patients Based on UPLC-Q-TOF-MS and Machine Learning Approach.

Chem Res Toxicol 2019 Mar 11. Epub 2019 Mar 11.

College of Physics and Electronic Information Engineering , Wenzhou University , Wenzhou 325035 , China.

Most paraquat (PQ) poisoned patients died from acute multiple organ failure (MOF) such as lung, kidney, and heart. However, the exact mechanism of intoxication is still unclear. In order to find out the initial toxic mechanism of PQ poisoning, a blood metabolomics study based on ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and efficient machine learning approach was performed on 23 PQ poisoned patients and 29 healthy subjects. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00328DOI Listing
March 2019
2 Reads

Impact of DNA Oxidation on Toxicology: From Quantification to Genomics.

Chem Res Toxicol 2019 Feb 26. Epub 2019 Feb 26.

Department of Chemistry , University of Utah , Salt Lake City , Utah 84112-0850 , United States.

Understanding the toxicological implications of deoxyribonucleic acid (DNA) oxidation arising from cellular oxidative stress depends on identifying DNA oxidation products, their location in the genome, and their interaction with repair, replication, and gene expression. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00046DOI Listing
February 2019
1 Read

Carcinogenic Metabolic Activation Process of Naphthalene by the Cytochrome P450 Enzyme 1B1: A Computational Study.

Chem Res Toxicol 2019 Mar 1. Epub 2019 Mar 1.

Environment Research Institute , Shandong University , Qingdao 266237 , People's Republic of China.

The metabolic activation and transformation of naphthalene by the cytochrome P450 enzyme (CYP 1B1) plays an important role in its potential carcinogenicity. The process has been explored by a quantum mechanics/molecular mechanics (QM/MM) computational method. Molecular dynamic simulations were performed to explore the interaction between naphthalene and CYP 1B1. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00297DOI Listing
March 2019
1 Read

Impact of CH223191-induced mitochondrial dysfunction on its aryl hydrocarbon receptor agonistic and antagonistic activities.

Chem Res Toxicol 2019 Feb 22. Epub 2019 Feb 22.

The mechanisms underlying aryl hydrocarbon receptor (AHR) activation by agonists and circumstances that increase the sensitivity toward agonists and AHR inhibition by antagonists are diverse and still not fully understood. AHR antagonist, 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide, CH223191, has been reported to inhibit the AHR transcription activity. However, CH223191 antagonist activity toward an AHR endogenous ligand, 6-formylindolo[3,2-b]carbazole (FICZ), and its mode of action remain to be elusive. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00371DOI Listing
February 2019
1 Read
3.529 Impact Factor

Measuring the Interaction of Transcription Factor Nrf2 with Its Negative Regulator Keap1 in Single Live Cells by an Improved FRET/FLIM Analysis.

Chem Res Toxicol 2019 Mar 11. Epub 2019 Mar 11.

Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine , University of Dundee , Dundee DD1 9SY , Scotland , United Kingdom.

Transcription factor NF-E2 p45-related factor 2 (Nrf2) and its principal negative regulator, Kelch-like ECH-associated protein 1 (Keap1), comprise a molecular effector and sensor system that robustly responds to perturbations of the cellular redox homeostasis by orchestrating a comprehensive cytoprotective program. Under homeostatic conditions, Nrf2 is a short-lived protein, which is targeted for ubiquitination and proteasomal degradation. Upon encounter of electrophiles, oxidants, or pro-inflammatory stimuli, the cysteine sensors in Keap1 are chemically modified, rendering Keap1 unable to target Nrf2 for degradation, and consequently leading to accumulation of the transcription factor and enhanced transcription of cytoprotective genes. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00354DOI Listing
March 2019
1 Read

Adduct Fluorescence as a Tool to Decipher Sequence Impact on Frameshift Mutations Mediated by a C-Linked C8-Biphenyl-Guanine Lesion.

Chem Res Toxicol 2019 Feb 20. Epub 2019 Feb 20.

Aromatic chemicals can undergo metabolic activation to afford electrophilic species that react at the C8-site of 2'-deoxyguanosine (dG) to generate bulky C8-dG adducts as a basis of initiating carcinogenesis. These DNA lesions have served as models to understand the mechanism of frameshift mutagenesis, especially within CG-dinucleotide repeat sequences, such as NarI (5'-GGCXCC-3', where X = C8-dG adduct). However, there is still limited capacity to predict the likelihood of mutation arising within particular contexts and hence chemistry-based strategies are needed for probing relationships between nucleic acid sequence and structure with replication errors. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00016DOI Listing
February 2019

Pyrimidine Ring-Opened Product from Oxidative DNA Damage of 5-Formyl-2'-deoxyuridine.

Chem Res Toxicol 2019 Feb 27. Epub 2019 Feb 27.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences , University of Occupational and Environmental Health , 807-8555 Kitakyushu , Japan.

After thymidine (dT) was treated with a Fenton-type reagent and further incubated for a long period (6 days) under physiological conditions (37 °C, pH 7.4), a new product, named dT*, was detected by HPLC in addition to the free thymine base and the known oxidative dT damage, 5-formyl-2'-deoxyuridine (fdU). dT* was found to be formed from fdU. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00401DOI Listing
February 2019

Triphenylphosphonium-Derived Protein Sulfenic Acid Trapping Agents: Synthesis, Reactivity, and Effect on Mitochondrial Function.

Chem Res Toxicol 2019 Mar 4. Epub 2019 Mar 4.

Department of Chemistry , Wake Forest University , Winston-Salem , North Carolina 27101 , United States.

Redox-mediated protein modifications control numerous processes in both normal and disease metabolism. Protein sulfenic acids, formed from the oxidation of protein cysteine residues, play a critical role in thiol-based redox signaling. The reactivity of protein sulfenic acids requires their identification through chemical trapping, and this paper describes the use of the triphenylphosphonium (TPP) ion to direct known sulfenic acid traps to the mitochondria, a verified source of cellular reactive oxygen species. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00385DOI Listing
March 2019
1 Read

RBOH-Dependent ROS Synthesis and ROS Scavenging by Plant Specialized Metabolites To Modulate Plant Development and Stress Responses.

Chem Res Toxicol 2019 Mar 11. Epub 2019 Mar 11.

Department of Biology and Centers for Molecular Signaling and Redox Biology and Medicine , Wake Forest University , Winston-Salem , North Carolina 27109 , United States.

Reactive oxygen species (ROS) regulate plant growth and development. ROS are kept at low levels in cells to prevent oxidative damage, allowing them to be effective signaling molecules upon increased synthesis. In plants and animals, NADPH oxidase/respiratory burst oxidase homolog (RBOH) proteins provide localized ROS bursts to regulate growth, developmental processes, and stress responses. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00028DOI Listing

Electron Deficiency of Nitro Group Determines Hepatic Cytotoxicity of Nitrofurantoin.

Chem Res Toxicol 2019 Feb 27. Epub 2019 Feb 27.

Wuya College of Innovation , Shenyang Pharmaceutical University , Shenyang , Liaoning 110016 , P. R. China.

Nitrofurantoin (NFT) is a widely used antimicrobial agent in the treatment of specific urinary tract infections (UTIs). Many adverse effects associated with NFT use have been reported, including hepatotoxicity. A structure-toxicity relationship study was performed to gain the insight into the mechanisms of toxic action of NFT. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00362DOI Listing
February 2019
3 Reads

Oxanosine Monophosphate Is a Covalent Inhibitor of Inosine 5'-Monophosphate Dehydrogenase.

Chem Res Toxicol 2019 Feb 25. Epub 2019 Feb 25.

Department of Chemistry , Brandeis University , Waltham , Massachusetts 02454 , United States.

Reactive nitrogen species (RNS) are produced during infection and inflammation, and the effects of these agents on proteins, DNA, and lipids are well recognized. In contrast, the effects of RNS damaged metabolites are less appreciated. 5-Amino-3-β-(d-ribofuranosyl)-3 H-imidazo-[4,5- d][1,3]oxazine-7-one (oxanosine) and its nucleotides are products of guanosine nitrosation. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00342DOI Listing
February 2019
2 Reads

Inorganic Arsenic as an Endocrine Disruptor: Modulation of the Glucocorticoid Receptor Pathway in Placental Cells via CpG Methylation.

Chem Res Toxicol 2019 Mar 4. Epub 2019 Mar 4.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health , University of North Carolina , Chapel Hill , North Carolina 27516 , United States.

Prenatal exposure to inorganic arsenic (iAs) has been associated with adverse developmental and reproductive outcomes. These outcomes may be tied to altered functionality of nuclear transcription factors such as the glucocorticoid receptor (GR) in the placenta and associated gene expression. The GR pathway is integral for proper fetal and placental development, and perturbations in this pathway may underlie observed associations between prenatal iAs exposure and adverse birth outcomes. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00352DOI Listing

Mass Spectrometric Quantitation of Pyridyloxobutyl DNA Phosphate Adducts in Rats Chronically Treated with N'-Nitrosonornicotine.

Chem Res Toxicol 2019 Feb 26. Epub 2019 Feb 26.

Masonic Cancer Center , University of Minnesota , Minneapolis , Minnesota 55455 , United States.

The tobacco-specific carcinogens N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) require metabolic activation to exert their carcinogenicity. NNN and NNK are metabolized to the same reactive diazonium ions, which alkylate DNA forming pyridyloxobutyl (POB) DNA base and phosphate adducts. We have characterized the formation of both POB DNA base and phosphate adducts in NNK-treated rats and the formation of POB DNA base adducts in NNN-treated rats. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00007DOI Listing
February 2019

Covalent Modification of Phosphatidylethanolamine by Benzyl Isothiocyanate and the Resultant Generation of Ethanolamine Adduct as Its Metabolite.

Chem Res Toxicol 2019 Feb 21. Epub 2019 Feb 21.

Graduate School of Human Science and Environment , University of Hyogo , Himeji , Hyogo 670-0092 , Japan.

Benzyl isothiocyanate (BITC), a dietary isothiocyanate (ITC) derived from cruciferous vegetables, has anticancer properties. It is believed that the ITC moiety (-N═C═S) that reacts predominantly with thiol compounds plays a central role in triggering the activities resulting from these properties. Recent studies have demonstrated that ITCs also covalently modify amino moieties in a protein. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00331DOI Listing
February 2019

Internalization of Titanium Dioxide Nanoparticles Is Mediated by Actin-Dependent Reorganization and Clathrin- and Dynamin-Mediated Endocytosis in H9c2 Rat Cardiomyoblasts.

Chem Res Toxicol 2019 Feb 25. Epub 2019 Feb 25.

Departamento de Fisiología , Instituto Nacional de Cardiología "Ignacio Chávez" , Ciudad de México 14080 , México.

Titanium dioxide nanoparticles (TiO NPs) are widely used for industrial and commercial applications. Once inside the body, they translocate into the bloodstream and reach different areas of the cardiovascular system including the heart, increasing the risk of developing cardiovascular diseases; consequently, the investigation of their interaction with cardiac cells is required. We previously showed that TiO NPs are internalized by H9c2 rat cardiomyoblasts, and here, we examined the molecular mechanisms underlying this process. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00284DOI Listing
February 2019
2 Reads

Toxicokinetics of Chiral PCB 136 and Its Hydroxylated Metabolites in Mice with a Liver-Specific Deletion of Cytochrome P450 Reductase.

Chem Res Toxicol 2019 Feb 20. Epub 2019 Feb 20.

Department of Occupational and Environmental Health, College of Public Health , University of Iowa , Iowa City , Iowa 52242 , United States.

Exposure to polychlorinated biphenyls (PCBs) has been implicated in adverse human health effects, including developmental neurotoxicity. Several neurotoxic PCBs are chiral and undergo atropisomeric enrichment in vivo due to atropselective metabolism by cytochrome P450 enzymes. Here we study how the liver-specific deletion of the cytochrome P450 reductase ( cpr) gene alters the toxicokinetics of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in mice. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00389DOI Listing
February 2019
1 Read

Metabolism of Cyanide by Glutathione To Produce the Novel Cyanide Metabolite 2-Aminothiazoline-4-oxoaminoethanoic Acid.

Chem Res Toxicol 2019 Feb 21. Epub 2019 Feb 21.

Department of Chemistry and Biochemistry , South Dakota State University , Box 2202, Brookings , South Dakota 57007 , United States.

The direct analysis of cyanide (HCN or CN inclusively symbolized as CN) to confirm exposure has major limitations due to cyanide's volatility, reactivity, and short half-life in biological fluids. These limitations have led to the exploration of cyanide detoxification products for indirect verification of cyanide exposure. Although cyanide interacts strongly with sulfur-containing molecules, to date, biomarkers resulting from the interaction of cyanide with glutathione (GSH; i. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00384DOI Listing
February 2019

Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure?

Chem Res Toxicol 2019 Feb 18. Epub 2019 Feb 18.

Department of Public Health , University of Massachusetts , Lowell , Massachusetts 01854 , United States.

Biomonitoring of methylene diphenyl diisocyanate (MDI) in urine may be useful in industrial hygiene and exposure surveillance approaches toward disease (occupational asthma) prevention and in understanding pathways by which the internalized chemical is excreted. We explored possible urine biomarkers of MDI exposure in mice after respiratory tract exposure to MDI, as glutathione (GSH) reaction products (MDI-GSH), and after skin exposure to MDI dissolved in acetone. LC-MS analyses of urine identified a unique m/ z 543. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00262DOI Listing
February 2019
2 Reads
3.529 Impact Factor

Unveiling the Photophysical and Photochemical Reaction Process of Naproxen via Ultrafast Femtosecond to Nanosecond Laser Flash Photolysis.

Chem Res Toxicol 2019 Feb 15. Epub 2019 Feb 15.

Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province , Shantou University , Shantou 515063 , China.

Naproxen is a nonsteroidal anti-inflammatory drug that exhibits phototoxic side effects in humans, but its mechanism of phototoxicity is ambiguous. To uncover photophysical and photochemical reaction processes of naproxen, femtosecond to nanosecond transient absorption spectroscopies were employed to directly detect excited and transient states of naproxen upon UV irradiation in pure acetonitrile, acetonitrile:water 1:1, and acetonitrile:PBS 1:1 solutions. The transient absorption data together with time-dependent density functional theory analysis-predicted absorption spectra of selected intermediates were integrated to elucidate photochemical mechanisms for reactions of naproxen in different solutions. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00310DOI Listing
February 2019

Wood and Biomass Smoke: Addressing Human Health Risks and Exposures.

Chem Res Toxicol 2019 Feb 5;32(2):219-221. Epub 2019 Feb 5.

Department of Pharmacology and Toxicology, Center for Human Toxicology , University of Utah , 30 South 2000 East , Salt Lake City , Utah 84112 , United States.

Air pollutants from burning wood and biomass pose serious human health risks. Recent discoveries link the chemistry of smoke emissions with biochemical sensors and biological effect mediators. Strategic thinking of complex underlying factors is needed to protect people from harm. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00318DOI Listing
February 2019

Working Together: Redox Signaling between the Endoplasmic Reticulum and Mitochondria.

Chem Res Toxicol 2019 Feb 5. Epub 2019 Feb 5.

Department of Molecular Medicine , Cornell University , Ithaca , New York 14853 , United States.

The concept that reactive oxygen species (ROS) are primarily toxic, mitochondria-generated molecules has persisted for decades. Here we highlight the emerging complexity for ROS-based events, emphasizing the evolving importance of the endoplasmic reticulum as a source and platform for redox signaling. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00379DOI Listing
February 2019

Interaction of Quinone-Related Electron Acceptors with Hydropersulfide NaS: Evidence for One-Electron Reduction Reaction.

Chem Res Toxicol 2019 Feb 15. Epub 2019 Feb 15.

Environmental Biology Section, Faculty of Medicine , University of Tsukuba , 1-1-1 Tennodai , Tsukuba , Ibaraki 305-8575 , Japan.

We previously reported that 9,10-phenanthraquinone (9,10-PQ), an atmospheric electron acceptor, undergoes redox cycling with dithiols as electron donors, resulting in the formation of semiquinone radicals and monothiyl radicals; however, monothiols have little reactivity. Because persulfide and polysulfide species are highly reducing, we speculate that 9,10-PQ might undergo one-electron reduction with these reactive sulfides. In the present study, we explored the redox cycling capability of a variety of quinone-related electron acceptors, including 9,10-PQ, during interactions with the hydropersulfide NaS and its related polysulfides. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00158DOI Listing
February 2019

Quantification of DNA Lesions Induced by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Mammalian Cells.

Chem Res Toxicol 2019 Feb 15. Epub 2019 Feb 15.

Quantitative measurement of DNA adducts in carcinogen-exposed cells provides the information about the frequency of formation and the rate of removal of DNA lesions in vivo, which yields insights into the initial events of mutagenesis. Metabolic activation of tobacco-specific nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its reduction product 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), leads to pyridyloxobutylation and pyridylhydroxybutylation of DNA. In this study, we employed a highly robust nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry (nLC-nESI-MS/MS) coupled with the isotope-dilution method for simultaneous quantification of O-[4-(3-pyridyl)-4-hydroxylbut-1-yl]-2'-deoxyguanosine ( O-PHBdG) and O- and O-[4-(3-pyridyl)-4-hydroxylbut-1-yl]-thymidine ( O-PHBdT and O-PHBdT). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00374DOI Listing
February 2019

BDE-47 decreases progesterone levels in BeWo cells by interfering with mitochondrial functions and genes related to cholesterol transport.

Chem Res Toxicol 2019 Feb 4. Epub 2019 Feb 4.

Polybrominated diphenyl ethers (PBDEs) have been reported to exert reproductive endocrine toxicity, but the mechanisms for this process remain unclear. Currently available studies have concentrated on the enzymatic reactions during steroidogenesis, but the results are not consistent. In this study, we explored the effects of 2,2',4,4'-tertrabromodiphenyl ether (BDE-47) on progesterone biosynthesis and the potential mechanisms in human placental choriocarcinoma cells. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00312DOI Listing
February 2019
1 Read

Oxidative Response and Micronucleus Centromere Assay in HEp-2 Cells Exposed to Fungicide Iprodione.

Chem Res Toxicol 2019 Feb 14. Epub 2019 Feb 14.

GIBE (Grupo de Investigación en Biología Evolutiva), FCEyN-UBA, Facultad de Ciencias Exactas y Naturales, Instituto de Ecología, Genética y Evolución de Buenos Aires - Consejo de Investigaciones Científicas y Técnicas) , Universidad de Buenos Aires (IEGEBA-CONICET) , Ciudad Universitaria, Pabellón II, 4° Piso Laboratories. 43-46 , C1428EGA Buenos Aires , Argentina.

The fungicide agents are a key component in the fruits and vegetables production. The Iprodione residues are one of the pesticide more frequently found in food products. The available data about the cytotoxicity of iprodione and its metabolites are scarce and do not allow characterization of its genotoxic potential and define the risk assessment. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00405DOI Listing
February 2019
2 Reads

Aromatic Residues at the Dimer-Dimer Interface in the Peroxiredoxin Tsa1 Facilitate Decamer Formation and Biological Function.

Chem Res Toxicol 2019 Feb 11. Epub 2019 Feb 11.

Biochemistry & Molecular Biology Program, Departments of Biology and Chemistry , The College of Wooster , Wooster , Ohio 44691 , United States.

To prevent the accumulation of reactive oxygen species and limit associated damage to biological macromolecules, cells express a variety of oxidant-detoxifying enzymes, including peroxiredoxins. In Saccharomyces cerevisiae, the peroxiredoxin Tsa1 plays a key role in peroxide clearance and maintenance of genome stability. Five homodimers of Tsa1 can assemble into a toroid-shaped decamer, with the active sites in the enzyme being shared between individual dimers in the decamer. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00346DOI Listing
February 2019

Glutamine-451 Confers Sensitivity to Oxidative Inhibition and Heme-Thiolate Sulfenylation of Cytochrome P450 4B1.

Chem Res Toxicol 2019 Feb 11. Epub 2019 Feb 11.

Department of Biochemistry , Vanderbilt University School of Medicine , Nashville , Tennessee 37232-0146 , United States.

Human cytochrome P450 (P450) family 4 enzymes are involved in the metabolism of fatty acids and the bioactivation of carcinogenic arylamines and toxic natural products, e.g., 4-ipomeanol. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00353DOI Listing
February 2019

Carnosine and Carcinine Derivatives Rapidly React with Hypochlorous Acid to Form Chloramines and Dichloramines.

Chem Res Toxicol 2019 Feb 15. Epub 2019 Feb 15.

The Heart Research Institute , Newtown , New South Wales 2042 , Australia.

Hypochlorous acid (HOCl) is a highly reactive, toxic species generated by neutrophils via the action of myeloperoxidase in order to destroy invading pathogens. However, when HOCl is produced inappropriately, it can damage host tissue and proteins and plays a role in the initiation and progression of disease. Carnosine, a peptide of β-alanine and histidine, has been shown to react rapidly with HOCl yielding monochloramines and can undergo intramolecular transchlorination. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00363DOI Listing
February 2019

Excision of Oxidatively Generated Guanine Lesions by Competing Base and Nucleotide Excision Repair Mechanisms in Human Cells.

Chem Res Toxicol 2019 Feb 8. Epub 2019 Feb 8.

Chemistry Department , New York University , 31 Washington Place , New York , New York 10003-5180 , United States.

The interchange between different repair mechanisms in human cells has long been a subject of interest. Here, we provide a direct demonstration that the oxidatively generated guanine lesions spiroiminodihydantoin (Sp) and 5-guanidinohydantoin (Gh) embedded in double-stranded DNA are substrates of both base excision repair (BER) and nucleotide excision repair (NER) mechanisms in intact human cells. Site-specifically modified, P-internally labeled double-stranded DNA substrates were transfected into fibroblasts or HeLa cells, and the BER and/or NER mono- and dual incision products were quantitatively recovered after 2-8 h incubation periods and lysis of the cells. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00411DOI Listing
February 2019

Squalene Oxidation Induced by Urban Pollutants: Impact on Skin Surface Physico-Chemistry.

Chem Res Toxicol 2019 Feb 4;32(2):285-293. Epub 2019 Feb 4.

UNILEHAVRE, FR 3038 CNRS, URCOM, EA 3221 , Normandie University, France , 25 rue Philippe Lebon BP 1123 , 76063 Le Havre cedex , France.

The effect of urban pollutants on skin properties has been revealed through several epidemiological studies. However, comprehension of involved mechanisms remains undetermined. In addition, the impact of such stressors on skin surface properties, especially skin physico-chemistry, has not been investigated. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00311DOI Listing
February 2019
5 Reads

The Uptake and Release of Polysulfur Cysteine Species by Cells: Physiological and Toxicological Implications.

Chem Res Toxicol 2019 Feb 7. Epub 2019 Feb 7.

Environmental Biology Section, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki 305-8575 , Japan.

Hydropersulfides and related polysulfides have recently become topics of significant interest due to their physiological prevalence and proposed biological functions. Currently, examination of the effects of hydropersulfide treatment on cells is difficult due to their lack of inherent stability with respect to disproportionation. Herein, it is reported that the treatment of a variety of cell types with cysteine trisulfide (also known as thiocystine; Cys-SSS-Cys), results in an increase in intracellular hydropersulfide levels (e. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00340DOI Listing
February 2019

Chemical Reactivity of Aloe-Emodin and Its Hydroxylation Metabolites to Thiols.

Chem Res Toxicol 2019 Feb 6;32(2):234-244. Epub 2019 Feb 6.

Wuya College of Innovation , Shenyang Pharmaceutical University , Shenyang , Liaoning 110016 , P.R. China.

Aloe-emodin (AE), an anthraquinone derivative, is a bioactive ingredient isolated from rhubarb which is used to treat inflammatory illnesses in China and many other countries in Asia. AE has shown a wide range of pharmacological effects. Recent studies showed that exposure to AE could cause DNA damage and cytotoxicity. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00248
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http://dx.doi.org/10.1021/acs.chemrestox.8b00248DOI Listing
February 2019
8 Reads

Orlistat Displays Antitumor Activity and Enhances the Efficacy of Paclitaxel in Human Hepatoma Hep3B Cells.

Chem Res Toxicol 2019 Feb 22;32(2):255-264. Epub 2019 Jan 22.

School of Pharmacy , China Medical University , Taichung 404 , Taiwan.

Orlistat has been proved to be an effective fatty acid synthase inhibitor that is able to inhibit the proliferation and induce apoptosis in many cancer cell types. However, the anticancer effects of orlistat on hepatocellular carcinoma are undefined. We found that orlistat inhibited cell growth and induced G0/G1 cell cycle arrest with increased cyclin D, cyclin E, and p21 expression in human hepatoma Hep3B cells. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00269DOI Listing
February 2019

Nickel Oxide Nanoparticles Trigger Caspase- and Mitochondria-Dependent Apoptosis in the Yeast Saccharomyces cerevisiae.

Chem Res Toxicol 2019 Feb 4;32(2):245-254. Epub 2019 Feb 4.

Bioengineering Laboratory-CIETI, Chemical Engineering Department , ISEP-School of Engineering of Polytechnic Institute of Porto , Rua Dr António Bernardino de Almeida, 431 , 4249-015 Porto , Portugal.

The expansion of the industrial use of nickel oxide (NiO) nanoparticles (NPs) raises concerns about their potential adverse effects. Our work aimed to investigate the mechanisms of toxicity induced by NiO NPs, using the yeast Saccharomyces cerevisiae as a cell model. Yeast cells exposed to NiO NPs exhibited typical hallmarks of regulated cell death (RCD) by apoptosis [loss of cell proliferation capacity (cell viability), exposure of phosphatidylserine at the outer cytoplasmic membrane leaflet, nuclear chromatin condensation, and DNA damage] in a process that required de novo protein synthesis. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00265DOI Listing
February 2019
6 Reads

Carbon Monoxide and Small Hydrocarbon Emissions from Sub-ohm Electronic Cigarettes.

Chem Res Toxicol 2019 Feb 4;32(2):312-317. Epub 2019 Feb 4.

Chemistry Department, Faculty of Arts and Sciences , American University of Beirut , Beirut 1107 2020 , Lebanon.

Electronic cigarettes (ECIGs) are routinely advertised as a safer alternative to combustible cigarettes. ECIGs have been shown to emit less toxicants than conventional cigarettes. This study presents for the first time the mouthpiece emissions of carbon monoxide (CO) and small hydrocarbon gases, in addition to carbonyls, from a rebuildable atomizer sub-ohm device (SOD). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00324DOI Listing
February 2019
1 Read
3.529 Impact Factor

Ferroptosis: The Greasy Side of Cell Death.

Chem Res Toxicol 2019 Jan 31. Epub 2019 Jan 31.

Theodor-Boveri-Institute, Biocenter , University of Würzburg , 97074 Würzburg , Germany.

Ferroptosis is a form of cell death that requires phospholipid peroxidation and has attracted increased attention, both as a means to eradicate tumors resistant to standard chemotherapy and for its potential contribution to tissue damage such as in ischemia/reperfusion. The center stage taken by phospholipid peroxidation in ferroptosis is highlighted by recent discoveries that demonstrate an intricate regulation of both the metabolism of polyunsaturated fatty acids as well as mechanisms leading to their oxidation. These metabolic steps converge at the point of ferroptosis execution through mechanisms that are now only starting to be understood. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00349DOI Listing
January 2019
2 Reads
3.529 Impact Factor

Steady-State Human Pharmacokinetics of Monobutyl Phthalate Predicted by Physiologically Based Pharmacokinetic Modeling Using Single-Dose Data from Humanized-Liver Mice Orally Administered with Dibutyl Phthalate.

Chem Res Toxicol 2019 Feb 5;32(2):333-340. Epub 2019 Feb 5.

Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo 194-8543 , Japan.

Dibutyl phthalate (DBP) was widely used as a plasticizer but it has been recently replaced with other kinds of phthalates such as di(2-ethylhexyl)phthalate and diisononyl phthalate because of its toxicity. To evaluate the human risk of DBP, forward and reverse dosimetry was conducted using in silico simplified physiologically based pharmacokinetic (PBPK) modeling based on in vivo experimental pharmacokinetic data in humanized-liver mice (HL-mice) obtained after an oral dose of 100 mg/kg. Absorbed DBP was converted to monobutyl phthalate (MBP) and its glucuronide extensively in vivo. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00361DOI Listing
February 2019
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Analysis of Acrolein-Derived 1, N-Propanodeoxyguanosine Adducts in Human Lung DNA from Smokers and Nonsmokers.

Chem Res Toxicol 2019 Feb 30;32(2):318-325. Epub 2019 Jan 30.

Masonic Cancer Center , University of Minnesota , Minneapolis , Minnesota 55455 , United States.

Acrolein, the simplest α,β-unsaturated aldehyde, is present in relatively large quantities in cigarette smoke, and several studies have raised the possibility of it being a major etiological agent for smoking-related lung cancer. Acrolein reacts directly with DNA to form primarily Acr-dGuo adducts, which serve as important biomarkers for the assessment of exposure to acrolein and its potential role in smoking-related lung cancer. In this study, we developed an ultrasensitive and low-artifact method using liquid chromatography-nanoelectrospray ionization-high-resolution tandem mass spectrometry to quantitate Acr-dGuo adducts in normal lung tissue DNA obtained at surgery from lung cancer patients who never smoked and from those who continued smoking until surgery, as confirmed by urinary total cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00326DOI Listing
February 2019
1 Read
3.529 Impact Factor