6,050 results match your criteria Chemical Research in Toxicology [Journal]


Density Functional Theory in the Prediction of Mutagenicity: A Perspective.

Chem Res Toxicol 2020 Jul 9. Epub 2020 Jul 9.

As a field, computational toxicology is concerned with using in silico models to predict and understand the origins of toxicity. It is fast, relatively inexpensive and avoids the ethical conundrum of using animals in scientific experimentation. In this perspective, we discuss the importance of computational models in toxicology, with a specific focus on the different model types that can be used in predictive toxicological approaches (SARs and QSARs). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00113DOI Listing

Teneligliptin promotes bile acid synthesis and attenuates Lipid Accumulation in Obese Mice by targeting the KLF15-Fgf15 pathway.

Chem Res Toxicol 2020 Jul 8. Epub 2020 Jul 8.

Bile acids (BAs) play essential physiological roles not only by facilitating the absorption and transport of nutrients but also by acting as a complex molecular signaling system. Reduced levels of BAs have been observed in obesity and other metabolic disorders. In the present study, we explored the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin on BA synthesis, both in vitro and in vivo. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00192DOI Listing

Systems toxicology approach for testing chemical cardiotoxicity in larval zebrafish.

Chem Res Toxicol 2020 Jul 8. Epub 2020 Jul 8.

Transcriptomic approaches can give insight into molecular mechanisms underlying chemical toxicity and are increasingly being used as part of toxicological assessments. To aid the interpretation of transcriptomic data we have developed a systems toxicology method that relies on a computable biological network model. We created the first network model describing cardiotoxicity in zebrafish larvae - a valuable emerging model species in testing cardiotoxicity associated with drugs and chemicals. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00095DOI Listing
July 2020
3.529 Impact Factor

Quantitative Liquid Chromatography-Nanoelectrospray Ionization-High Resolution Tandem Mass Spectrometry Analysis of Acrolein-DNA Adducts and Etheno-DNA Adducts in Oral Cells from Cigarette Smokers and Non-smokers.

Chem Res Toxicol 2020 Jul 8. Epub 2020 Jul 8.

Cigarette smoking is an important source of human exposure to toxicants and carcinogens and contributes significantly to cancer morbidity and mortality worldwide. Acrolein, a widespread environmental pollutant, is present in relatively high amounts in cigarette smoke and can react directly with DNA to form DNA adducts, which serve as important biomarkers for the assessment of exposure to acrolein and its potential role in smoking related cancer. Etheno-DNA adducts are promutagenic DNA lesions that can derive from exogenous chemicals as well as endogenous sources, including lipid peroxidation. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00223DOI Listing

Three Human Pol Variants with Impaired Polymerase Activity Fail to Rescue HO Sensitivity in -Deficient Cells.

Chem Res Toxicol 2020 Jul 8. Epub 2020 Jul 8.

Human Y-family DNA polymerase (pol) is involved in translesion DNA synthesis (TLS) and base excision repair (BER) of oxidative DNA damage. Genetic variations may alter the function of pol and affect cellular susceptibility to oxidative genotoxic agents, but their effects remain unclear. We investigated the impacts of ten human missense germline variations on pol function by biochemical and cell-based assays. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00127DOI Listing

Hot wires and film boiling: Another look at carbonyl formation in electronic cigarettes.

Chem Res Toxicol 2020 Jul 8. Epub 2020 Jul 8.

Electronic cigarettes (ECIGS) are a class of tobacco products that emit a nicotine-containing aerosol by heating and vaporizing a liquid. Apart from initiating nicotine addiction in nonsmokers, a persistent concern about these products is that their emissions often include high levels of carbonyl species, toxicants thought to cause most non-cancer pulmonary disease in smokers. This study examined whether the phenomenon of film boiling can account for observations of high carbonyl emissions under certain operating conditions, and if so, whether film boiling theory can be invoked to predict conditions where high carbonyl emissions are likely. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00196DOI Listing

LC-MS/MS Coupled with a Stable-Isotope Dilution Method for the Quantitation of Thioproline-Glycine: A Novel Metabolite in Formaldehyde- and Oxidative Stress-Exposed Cells.

Chem Res Toxicol 2020 Jul 7. Epub 2020 Jul 7.

Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.

Formaldehyde (FA) is a human carcinogen that is ubiquitous in the ambient environment and also generated endogenously in oxidatively stressed cells. There is accumulated evidence that FA is an etiological agent of leukemia development in humans. To develop a biomarker for FA exposure, we have, in this study, developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with stable isotope-dilution method to explore the reactivity of FA with glutathione (GSH) in physiologically relevant conditions. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00170DOI Listing

Cytochrome P450 3A4-Mediated Bioactivation and its Role in Nomilin-Induced Hepatotoxicity.

Chem Res Toxicol 2020 Jul 7. Epub 2020 Jul 7.

Nomilin is a furan-containing triterpenoid isolated from the medicinal plants of Citrus. The aim of this study was to investigate the in vitro and in vivo bioactivation of nomilin and the role in nomilin-induced hepatotoxicity. Microsomal incubations of nomilin supplemented with NADPH and GSH or NAL resulted in the detection of six conjugates (M1-M6). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00228DOI Listing

The chlorination of N-methyl amino acids with hypochlorous acid: kinetics and mechanisms.

Chem Res Toxicol 2020 Jul 7. Epub 2020 Jul 7.

The formation and decomposition kinetics of N-chloro-N-methyl amino acids were studied to predict the fate and impact of these compounds in water treatment technologies and biological systems. These compounds form in fast second order reactions between N-methyl amino acids and hypochlorous acid. The comparison of the activation parameters for the reactions of N-methyl substituted and non-substituted branched chain amino acids reveals the transition state features less organized structure and stronger bonds between the reactants in the reactions with the N-methyl derivatives. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00222DOI Listing

Metabolic Interaction between Ammonia and Baicalein.

Chem Res Toxicol 2020 Jul 3. Epub 2020 Jul 3.

Ammonia is treated as a primary waste product of cellular metabolism in vivo and can contribute to the alteration of neurotransmission, oxidative stress, and cerebral edema and astrocyte swelling when its concentration in the brain is high. The objective of this study was to determine whether bioactive polyphenol baicalein had the capacity to trap ammonia in vitro and in vivo. Under in vitro conditions, baicalein rapidly reacted with ammonia to generate two mono-aminated products and one di-aminated product under different reaction times. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00205DOI Listing

Chemical and toxicological characterization of vaping emission products from commonly used vape juice diluents.

Chem Res Toxicol 2020 Jul 3. Epub 2020 Jul 3.

Recent reports have linked severe lung injuries and deaths to the use of e-cigarettes and vaping products. Nevertheless, the causal relationship between exposure to vaping emissions and the observed health outcomes remains to be elucidated. Through chemical and toxicological characterization of vaping emission products, this study demonstrates that during vaping processes, changes in chemical composition of several commonly used vape juice diluents (also known as cutting agents) lead to the formation of toxic byproducts, including quinones, carbonyls, esters and alkyl alcohols. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00174DOI Listing

Microcystins: biogenesis, toxicity, analysis and control.

Chem Res Toxicol 2020 Jul 2. Epub 2020 Jul 2.

Microcystins are cyclic peptide toxins formed by cyanobacteria. These toxins are recognized for their association with algal blooms, posing a significant threat to ecosystems and drinking water quality. Due to the growing environmental concerns they raise, a comprehensive review on microcystins' genesis, toxicity, and analytical methods for their quantitative determination is outlined. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00164DOI Listing

Thermodynamic parameters at bio-nano interface and nanomaterial toxicity: A case study on BSA interaction with ZnO, SiO and TiO.

Chem Res Toxicol 2020 Jun 29. Epub 2020 Jun 29.

Understanding the nanomaterial (NM) - protein interactions is a key issue in defining the bio-reactivity of NMs with great impact for nanosafety. In the present work, the complex phenomena occurring at the bio/nano interface were evaluated in a simple case study focusing on NM-protein binding thermodynamics and protein stability for three representative metal oxide NMs, namely zinc oxide (ZnO) (NM-110), titanium dioxide (TiO2) (NM-101) and silica (SiO2) (NM-203), The thermodynamic signature associated with the NM interaction with an abundant protein occurring in most cell culture media, bovine serum albumin (BSA), has been investigated by isothermal titration and differential scanning calorimetry. Circular Dichroism spectroscopy offered additional information concerning adsorption-induced protein conformational changes. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00468DOI Listing

1-Formyl-7-hydroxy-6,7-dihydro-5-pyrrolizine (1-CHO-DHP)-Cysteine Conjugates: Metabolic Formation and Binding to Cellular DNA.

Chem Res Toxicol 2020 Jul 10. Epub 2020 Jul 10.

National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States.

1-Formyl-7-hydroxy-6,7-dihydro-5-pyrrolizine (1-CHO-DHP) is a potential proximate carcinogenic metabolite of pyrrolizidine alkaloids. In the present study, we determined that the reaction of 1-CHO-DHP with cysteine generated four identified products. By mass and H NMR spectral analyses, these products are cysteinyl-[2'--7]-1-CHO-DHP (P2), cysteinyl-[3'--7]-1-CHO-DHP (P3), 7-keto-DHP (P4), and 1-cysteinylimino-DHP (P5). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00143DOI Listing

Gas Chromatography-Tandem Mass Spectrometry Verification of Sulfur Mustard Exposure in Humans through the Conversion of Protein Adducts to Free Sulfur Mustard.

Chem Res Toxicol 2020 Jul 7. Epub 2020 Jul 7.

U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, United States.

Exposures to sulfur mustard (HD; bis(2-chloroethyll) sulfide) are well-known to result in the formation of adducts with free aspartate and glutamate residues of plasma proteins (Lawrence, R. J., Smith, J. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00134DOI Listing

Exposure to the heavy metal lead induces DNA copy number alterations in zebrafish cells.

Chem Res Toxicol 2020 Jun 22. Epub 2020 Jun 22.

DNA copy number variants (CNVs) are associated with the development of complex neurological diseases and disorders including autism spectrum disorder, schizophrenia, Alzheimer's disease, and Parkinson's disease. Exposure to multiple environmental chemicals including various heavy metals is suggested as a risk factor in these neurological diseases and disorders, but few studies have addressed if heavy metal exposure can result in de novo DNA copy number changes as a genetic mechanism contributing to these disease outcomes. In this study to further investigate the relationship between heavy metal exposure and de novo copy number alterations (CNAs), zebrafish fibroblast cells were exposed to the neurotoxicant lead (Pb). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00156DOI Listing

PARP1 Is Required for ATM-Mediated p53 Activation and p53-Mediated Gene Expression after Ionizing Radiation.

Chem Res Toxicol 2020 Jul 7. Epub 2020 Jul 7.

Department of Food Chemistry and Toxicology, Institute of Applied Biosciences, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, 76131 Karlsruhe, Germany.

PARP1 and p53 are key players in maintaining genomic stability, but their interplay is still not fully understood. We investigated the impact of PARP1 knockout on the DNA damage response after ionizing radiation (IR) by comparing a U2OS-based PARP1-knockout cell line, established by using the genome-editing system CRISPR/Cas9, with its wild-type counterpart. We intended to gain more insight into the impact of PARP1 on the transcriptional level under basal conditions, after low dose (1 Gy) and high dose (10 Gy) DNA damage induced by IR, aiming to reveal the potential connections between the involved pathways. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00130DOI Listing

Site-Specific Incorporation of -(2'-Deoxyguanosine-8-yl)-6-aminochrysene Adduct in DNA and Its Replication in Human Cells.

Chem Res Toxicol 2020 Jul 7. Epub 2020 Jul 7.

Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.

The environmental pollutant 6-nitrochrysene (6-NC) is a potent mutagen and a mammary carcinogen in rats. 6-NC is the most potent carcinogen ever tested in the newborn mouse assay. In mammalian cells, it is metabolically activated by nitroreduction and a combination of ring oxidation and nitroreduction pathways. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00197DOI Listing

Metabolism and Toxicity of Emodin: Genome-Wide Association Studies Reveal Hepatocyte Nuclear Factor 4α Regulates UGT2B7 and Emodin Glucuronidation.

Chem Res Toxicol 2020 Jul 7. Epub 2020 Jul 7.

State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Southern Medical University, Guangzhou 510515, China.

Emodin is the main toxic component in Chinese medicinal herbs such as rhubarb. Our previous studies demonstrated that genetic polymorphisms of UDP-glucuronosyltransferase 2B7 (UGT2B7) had an effect on the glucuronidation and detoxification of emodin. This study aimed to reveal the transcriptional regulation mechanism of UGT2B7 on emodin glucuronidation and its effect on toxicity. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00047DOI Listing

Introduction to Special Issue: Environmental Toxicology.

Chem Res Toxicol 2020 Jun;33(6):1279-1280

Center for Public Health and Environmental Assessment, Reproductive Developmental Toxicology Branch, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, United States.

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http://dx.doi.org/10.1021/acs.chemrestox.0c00203DOI Listing

Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts.

Chem Res Toxicol 2020 Jun 29. Epub 2020 Jun 29.

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.

Albumin is an abundant protein in the lung lining fluid that forms an interface between lung epithelial cells and the external environment. In the lung, albumin can be targeted for adduction by inhaled acrolein. Acrolein, an α,β-unsaturated aldehyde, reacts with biomolecules via Michael addition at the β-carbon or Schiff base formation at the carbonyl carbon. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00146DOI Listing

Analysis of Biomarkers of DNA Damage and Mutagenicity in Mice Exposed to Acrylonitrile.

Chem Res Toxicol 2020 Jun 28. Epub 2020 Jun 28.

Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9, Canada.

Acrylonitrile (ACN), which is a widely used industrial chemical, induces cancers in the mouse via unresolved mechanisms. For this report, complementary and previously described methods were used to assess in vivo genotoxicity and/or mutagenicity of ACN in several mouse models, including (i) female mice devoid of cytochrome P450 2E1 (CYP2E1), which yields the epoxide intermediate cyanoethylene oxide (CEO), (ii) male transgenic mice, and (iii) female (wild-type) B6C3F1 mice. Exposures of wild-type mice and CYP2E1-null mice to ACN at 0, 2. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00154DOI Listing

Analysis of DNA Adducts and Mutagenic Potency and Specificity in Rats Exposed to Acrylonitrile.

Chem Res Toxicol 2020 Jun 28. Epub 2020 Jun 28.

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, United States.

Acrylonitrile (ACN), which is a widely used industrial chemical, induces cancers in multiple organs/tissues of rats by unresolved mechanisms. For this report, evidence for ACN-induced direct/indirect DNA damage and mutagenesis was investigated by assessing the ability of ACN, or its reactive metabolite, 2-cyanoethylene oxide (CEO), to bind to DNA in vitro, to form select DNA adducts [N7-(2'-oxoethyl)guanine, ,3-ethenoguanine, 1,-ethenodeoxyadenosine, and 3,-ethenodeoxycytidine] in vitro and/or in vivo, and to perturb the frequency and spectra of mutations in the hypoxanthine-guanine phosphoribosyltransferase () gene in rats exposed to ACN in drinking water. Adducts and frequencies and spectra of mutations were analyzed using published methods. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00153DOI Listing

New Perspectives on Drug-Induced Liver Injury Risk Assessment of Acyl Glucuronides.

Chem Res Toxicol 2020 Jun 29. Epub 2020 Jun 29.

PK Sciences, Novartis Institutes for Biomedical Research, Novartis Campus, 4052 Basel, Switzerland.

Drug-induced liver injury (DILI) remains one of the key challenges in drug development due to the mechanisms of action being multifactorial in nature. This is particularly the case for idiosyncratic DILI which occurs in a very low frequency in humans (e.g. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00131DOI Listing

Applications of CometChip for Environmental Health Studies.

Chem Res Toxicol 2020 Jun 10. Epub 2020 Jun 10.

Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

Environmental exposures have long been known to impact public health and safety. For example, exposures to airborne particulates, heavy metals in water, or certain industrial chemicals can contribute to aging and to risk of developing cancer and other diseases. Environmental factors can impact health in a variety of ways, but a key concern is DNA damage, which can lead to mutations that cause cancer. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00393DOI Listing

Integrated Proteomics and Metabolomics Reveal the Mechanism of Nephrotoxicity Induced by Triptolide.

Chem Res Toxicol 2020 Jun 10. Epub 2020 Jun 10.

Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin 301600, China.

Triptolide (TP), the main active ingredient of Tripterygium wilfordii Hook F., has great potential in the treatment of autoimmune diseases. However, it has been found that the side effects of TP involve multiple organs and systems, of which the most serious side effects relate to the kidney. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00091DOI Listing

Evidence for Polyamine, Biogenic Amine, and Amino Acid Adduction Resulting from Metabolic Activation of Diosbulbin B.

Chem Res Toxicol 2020 Jun 22. Epub 2020 Jun 22.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

L. (DBL), a traditional Chinese medicine, is a well-known herb with hepatotoxicity, and the biochemical mechanisms of the toxic action remain unknown. Diosbulbin B (DSB), a major component of DBL, can induce severer liver injury which requires cytochrome P450-catalyzed oxidation of the furan ring. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00017DOI Listing
June 2020
3.529 Impact Factor

Mesoporous Silica Nanoparticles at Predicted Environmentally Relevant Concentrations Cause Impairments in GABAergic Motor Neurons of Nematode .

Chem Res Toxicol 2020 Jun 18. Epub 2020 Jun 18.

Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P. R. China.

Available safety evaluations regarding mesoporous silica nanoparticles (mSiNPs) are based on the assumption of a relatively high exposure concentration, which makes the findings less valuable in a realistic environment. In this study, we employed () as a model to assess the neuronal damage caused by mSiNPs at the predicted environmentally relevant concentrations. After nematodes were acute and prolonged exposed to mSiNPs at concentrations over 300 μg/L, locomotion degeneration, shrinking behavior, and abnormal foraging behavior were observed, which were associated with the deficits in the development of GABAergic neurons, including D-type and RME motor neurons. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00477DOI Listing

Strategies to Mitigate the Bioactivation of Aryl Amines.

Chem Res Toxicol 2020 Jun 23. Epub 2020 Jun 23.

Genentech Inc., 1 DNA Way, South San Francisco, California 94080, United States.

The bioactivation of xenobiotics to yield reactive metabolites can lead to tolerability and toxicity concerns within a drug discovery program. Development of strategies for mitigating the metabolic liability of commonly encountered toxicophores, such as anilines, relies on an understanding of the relative tendency of these functionalities to undergo bioactivation. In this report, we present the first systematic study of the structure-activity relationships of the bioactivation of aryl amine fragments (molecular weight < 250 Da) using a glutathione (GSH) trapping assay in the presence of human liver microsomes and the reduced form of nicotinamide adenine dinucleotide phosphate. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00138DOI Listing

Physiologically Based Pharmacokinetic Models Predicting Renal and Hepatic Concentrations of Industrial Chemicals after Virtual Oral Doses in Rats.

Chem Res Toxicol 2020 Jun 19. Epub 2020 Jun 19.

Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, 3-3165 Higashi-tamagawa Gakuen, Machida, Tokyo 194-8543, Japan.

Recently developed high-throughput in vitro assays in combination with computational models could provide alternatives to animal testing. The purpose of the present study was to model the plasma, hepatic, and renal pharmacokinetics of approximately 150 structurally varied types of drugs, food components, and industrial chemicals after virtual external oral dosing in rats and to determine the relationship between the simulated internal concentrations in tissue/plasma and their lowest-observed-effect levels. The model parameters were based on rat plasma data from the literature and empirically determined pharmacokinetics measured after oral administrations to rats carried out to evaluate hepatotoxic or nephrotic potentials. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00009DOI Listing

Impact of E-Cigarette Liquid Flavoring Agents on Activity of Microsomal Recombinant CYP2A6, the Primary Nicotine-Metabolizing Enzyme.

Chem Res Toxicol 2020 Jun 18. Epub 2020 Jun 18.

Public Health and Integrative Toxicology Division, Office of Research and Development, United States Environmental Protection Agency, Chapel Hill, North Carolina 27514, United States.

Nicotine is the primary psychoactive chemical in both traditional and electronic cigarettes (e-cigarettes). Nicotine levels in both traditional cigarettes and e-cigarettes are an important concern for public health. Nicotine exposure due to e-cigarette use is of importance primarily due to the addictive potential of nicotine, but there is also concern for nicotine poisoning in e-cigarette users. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00514DOI Listing

Mitochondrial DNA Damage: Prevalence, Biological Consequence, and Emerging Pathways.

Chem Res Toxicol 2020 Jun 18. Epub 2020 Jun 18.

Department of Chemistry and Environmental Toxicology Graduate Program, University of California, Riverside, Riverside, California 92521, United States.

Mitochondria have a plethora of functions within a eukaryotic cell, ranging from energy production, cell signaling, and protein cofactor synthesis to various aspects of metabolism. Mitochondrial dysfunction is known to cause over 200 named disorders and has been implicated in many human diseases and aging. Mitochondria have their own genetic material, mitochondrial DNA (mtDNA), which encodes 13 protein subunits in the oxidative phosphorylation system and a full set of transfer and rRNAs. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00083DOI Listing

Cytochrome P450-Mediated Bioactivation: Implication for the Liver Injury Induced by Fraxinellone, A Bioactive Constituent from Dictamni Cortex.

Chem Res Toxicol 2020 Jun 8. Epub 2020 Jun 8.

Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.

Fraxinellone, a furanoid, is one of the bioactive and potentially hepatotoxic constituents from Turcz, which is extensively spread throughout Asian countries. This herb was reported to cause liver injury in clinical application. However, the mechanism behind is still not fully understood. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00141DOI Listing

Distinct Orchestration and Dynamic Processes on γ-H2AX and p-H3 for Two Major Types of Genotoxic Chemicals Revealed by Mass Spectrometry Analysis.

Chem Res Toxicol 2020 Jun 2. Epub 2020 Jun 2.

Genotoxic chemicals act by causing DNA damage, which, if left unrepaired, can have deleterious consequences for cell survival. DNA damage response (DDR) gets activated to repair or mitigate the effects of DNA damage. Histone H2AX and H3 phosphorylation biomarkers (γ-H2AX and p-H3) have attracted great attention as they play pivotal roles in the DDR. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00104DOI Listing

Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice.

Chem Res Toxicol 2020 Jun 11. Epub 2020 Jun 11.

Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States.

Our early studies demonstrated an impressive chemopreventive efficacy of dihydromethysticin (DHM), unique in kava, against tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice in which DHM was supplemented in the diet. The current work was carried out to validate the efficacy, optimize the dosing schedule, and further elucidate the mechanisms using oral bolus dosing of DHM. The results demonstrated a dose-dependent chemopreventive efficacy of DHM (orally administered 1 h before each of the two NNK intraperitoneal injections, 1 week apart) against NNK-induced lung adenoma formation. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00161DOI Listing

Reply to Letter to Editor from Veeravalli and Dash on "Tofacitinib Is a Mechanism-Based Inactivator of Cytochrome P450 3A4: Revisiting the Significance of the Epoxide Intermediate and Glutathione Trapping".

Chem Res Toxicol 2020 Jun 16. Epub 2020 Jun 16.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.

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http://dx.doi.org/10.1021/acs.chemrestox.0c00187DOI Listing

Predicting Uncoupling Toxicity of Organic Acids Based on Their Molecular Structure Using a Biophysical Model.

Chem Res Toxicol 2020 Jun 12. Epub 2020 Jun 12.

Analytical Environmental Chemistry, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany.

We present a purely mechanistic model to predict protonophoric uncoupling activity EC of organic acids. All required input information can be derived from their chemical structure. This makes it a convenient predictive model to gain valuable information on the toxicity of organic chemicals already at an early stage of development of new commercial chemicals (e. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00063DOI Listing

Mechanistic Insights on Skin Sensitization to Linalool Hydroperoxides: EPR Evidence on Radical Intermediates Formation in Reconstructed Human Epidermis and C NMR Reactivity Studies with Thiol Residues.

Chem Res Toxicol 2020 Jun 3. Epub 2020 Jun 3.

Dermatochemistry Laboratory, University of Strasbourg, CNRS, UMR 7177, F-67000 Strasbourg, France.

Linalool is one of the most commonly used fragrance terpenes in consumer products. While pure linalool is considered as non-allergenic because it has a very low skin sensitization potential, its autoxidation on air leads to allylic hydroperoxides that have been shown to be major skin sensitizers. These hydroperoxides have the potential to form antigens radical mechanisms. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00125DOI Listing

Polychlorinated Biphenyl Quinone Promotes Atherosclerosis through Lipid Accumulation and Endoplasmic Reticulum Stress via CD36.

Chem Res Toxicol 2020 Jun 29;33(6):1497-1507. Epub 2020 May 29.

College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.

Polychlorinated biphenyls (PCBs) are persistent organic environmental pollutants. According to previous epidemiological reports, PCBs exposure is highly related to atherosclerosis. However, studies of PCBs metabolites and atherosclerosis and corresponding mechanism studies are scarce. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00123DOI Listing

Free Radical Production and Characterization of Heat-Not-Burn Cigarettes in Comparison to Conventional and Electronic Cigarettes.

Chem Res Toxicol 2020 Jun 2. Epub 2020 Jun 2.

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.

With conventional cigarettes, the burning cone reaches temperatures of >900 °C, resulting in the production of numerous toxicants and significant levels of highly reactive free radicals. In attempts to eliminate combustion while still delivering nicotine and flavorings, a newer alternative tobacco product has emerged known as "heat-not-burn" (HnB). These products heat tobacco to temperatures of 250-350 °C depending on the device allowing for the volatilization of nicotine and flavorants while potentially limiting the production of combustion-related toxicants. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00088DOI Listing

Interactions of Perfluorooctanesulfonate and 6:2 Chlorinated Polyfluorinated Ether Sulfonate with Human Serum Albumin: A Comparative Study.

Chem Res Toxicol 2020 Jun 22;33(6):1478-1486. Epub 2020 May 22.

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.

6:2 Chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) possesses a similar structure to perfluorooctanesulfonate (PFOS) and is the third most important polyfluoroalkyl/perfluoroalkyl substance (PFAS) found in the general population of China. Studies have indicated that 6:2 Cl-PFESA exhibits a stronger bioaccumulative and toxicological potential than PFOS and is thus of considerable environmental concern. Here, the binding characteristics of PFOS and 6:2 Cl-PFESA to human serum albumin (HSA) were explored based on and methods. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00075DOI Listing

Special Issue on "Future Nanosafety".

Chem Res Toxicol 2020 May;33(5):1037-1038

INM - Leibniz-Institute for New Materials, Saarbrücken, Germany.

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http://dx.doi.org/10.1021/acs.chemrestox.0c00166DOI Listing

Arsenic Exposure and Compromised Protein Quality Control.

Chem Res Toxicol 2020 Jun 2. Epub 2020 Jun 2.

Exposure to arsenic in contaminated drinking water is a worldwide public health problem that affects more than 200 million people. Protein quality control constitutes an evolutionarily conserved mechanism for promoting proper folding of proteins, refolding of misfolded proteins, and removal of aggregated proteins, thereby maintaining homeostasis of the proteome (i.e. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00107DOI Listing

Ensemble Models Based on QuBiLS-MAS Features and Shallow Learning for the Prediction of Drug-Induced Liver Toxicity: Improving Deep Learning and Traditional Approaches.

Chem Res Toxicol 2020 May 14. Epub 2020 May 14.

Grupo de Investigación Prometeus & Biomedicina Aplicada a las Ciencias Clínicas, Área de Bioquímica, Campus de Zaragocilla, Facultad de Medicina, Universidad de Cartagena, Cartagena de Indias 130001, Colombia.

Drug-induced liver injury (DILI) is a key safety issue in the drug discovery pipeline and a regulatory concern. Thus, many tools have been proposed to improve the hepatotoxicity prediction of organic-type chemicals. Here, classifiers for the prediction of DILI were developed by using QuBiLS-MAS 0-2. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00030DOI Listing

Novel Poly(ADP-ribose) Polymerase-1 Inhibitor DDHCB Inhibits Proliferation of BRCA Mutant Breast Cancer Cell and through a Synthetic Lethal Mechanism.

Chem Res Toxicol 2020 May 21. Epub 2020 May 21.

Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.

Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are drugs that are effectively used to treat breast cancer. We synthesized a novel bromophenol derivative ethyl ()-4-(2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamido)benzoate (DDHCB) as a novel PARP-1 inhibitor. Our study found that DDHCB could inhibit PARP-1 activity with an IC value of 58. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00087DOI Listing

Biological Basis for Threshold Responses to Methylating Agents.

Authors:
Adam D Thomas

Chem Res Toxicol 2020 May 27. Epub 2020 May 27.

Centre for Research in Biosciences, University of the West of England, Frenchay Campus, Bristol BS16 1QY, United Kingdom.

The cellular outcomes of chemical exposure are as much about the cellular to the chemical as it is an of the chemical. We are growing in our understanding of the genotoxic interaction between chemistry and biology. For example, recent data has revealed the biological basis for mutation induction curves for a methylating chemical, which has been shown to be dependent on the repair capacity of the cells. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00052DOI Listing

Advanced Testing Strategies and Models of the Intestine for Nanosafety Research.

Chem Res Toxicol 2020 May 8;33(5):1163-1178. Epub 2020 May 8.

Leibniz Research Institute for Environmental Medicine, IUF, 40225 Düsseldorf, Germany.

There is growing concern about the potential adverse effects of oral exposure to engineered nanomaterials (ENM). Recent years have witnessed major developments in and advancement of intestinal models for nanosafety evaluation. The present paper reviews the key factors that should be considered for inclusion in nonanimal alternative testing approaches to reliably reflect the dynamics of the physicochemical properties of ENM as well the intestinal physiology and morphology. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00079DOI Listing

Thinking Outside the Cage: A New Hypothesis That Accounts for Variable Yields of Radicals from the Reaction of CO with ONOO.

Chem Res Toxicol 2020 May 20. Epub 2020 May 20.

Institute of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, CH-8093 Zürich, Switzerland.

In biology, the reaction of ONOO with CO is the main sink for ONOO. This reaction yields CO, NO, NO, and CO. There is a long-standing debate with respect to the yield of the radicals relative to ONOO. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00309DOI Listing

Correction to "Hemoglobin Adducts and Urinary Metabolites of Arylamines and Nitroarenes".

Chem Res Toxicol 2020 May 6. Epub 2020 May 6.

Institute of Environmental and Occupational Toxicology, Casella Postale 108, CH-6780 Airolo, Switzerland.

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http://dx.doi.org/10.1021/acs.chemrestox.0c00117DOI Listing