5,480 results match your criteria Chemical Research in Toxicology [Journal]


Molecular dynamics simulations of mismatched DNA duplexes associated with the major C-linked 2'-deoxyguanosine adduct of the food mutagen ochratoxin A: Influence of opposing base, adduct ionization state and sequence on the structure of damaged DNA.

Chem Res Toxicol 2018 Jun 20. Epub 2018 Jun 20.

Exposure to ochratoxin A (OTA) is associated with chronic renal diseases and carcinogenesis. The deleterious effects of OTA have been linked to its covalent binding at C8 position of guanine (G) to form DNA adduct (OT-G), which causes various mutations. To contribute towards understanding the complex mutagenic profile of OTA, the present work uses a robust computational approach to characterize post-replication DNA structures containing OT-G mismatched with canonical nucleobases. Read More

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Potential of the bio-inspired CaCO3 microspheres loaded with tetracycline in inducing differential cytotoxic effects towards non-cancerous and cancer cells: A cytogenetic toxicity assessment using CHO cells in vitro.

Chem Res Toxicol 2018 Jun 20. Epub 2018 Jun 20.

Calcium carbonate (CaCO3) based materials as feasible pH sensitive drug carriers which can actively dissolve in acidic microenvironment of cancer cells, are finding increasing importance. This has drawn our interest in the development of a bio-inspired polypeptide- mediated method to design calcium carbonate microspheres loaded with tetracycline (CaCO3-TC) with an aim to explore its safe application in cancer therapeutics. Its therapeutic application in cancer patients essentially demands its safety information on the normal cells. Read More

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The Quinone Based Antitumor Agent Sepantronium Bromide (YM155) Causes Oxygen Independent Redox Activated Oxidative DNA Damage.

Chem Res Toxicol 2018 Jun 13. Epub 2018 Jun 13.

Sepantronium bromide (YM155) is a small molecule antitumor agent currently in phase II clinical trials. Although developed as survivin suppressor, YM155's primary mode of action has recently been found to be DNA damage. However, the mechanism of DNA damage by YM155 is still unknown. Read More

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June 2018
3 Reads

Identification of novel pathways in idelalisib metabolism and bioactivation.

Chem Res Toxicol 2018 Jun 13. Epub 2018 Jun 13.

Idelalisib (ILB) is a selective phosphatidylinositol-3-kinase delta inhibitor approved for the treatment of hematological malignancies. However, ILB frequently causes hepatotoxicity and the exact mechanism remains unclear. The current study profiled the metabolites of ILB in mouse liver, urine and feces. Read More

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June 2018
1 Read

4-Hydroxy-7-oxo-5-heptenoic Acid (HOHA) Lactone is a Potent Inducer of the Complement Pathway in Human Retinal Pigmented Epithelial Cells.

Chem Res Toxicol 2018 Jun 8. Epub 2018 Jun 8.

We previously discovered that oxidative cleavage of docosahexaenoate (DHA), which is especially abundant in the retinal photoreceptor rod outer segments and retinal pigmented endothelial (RPE) cells, generates 4-hydroxy-7-oxo-5-heptenoate (HOHA) lactone, and that HOHA lactone can enter RPE cells that metabolize it through conjugation with glutathione (GSH). The consequent depletion of GSH results in oxidative stress. We now find that HOHA-lactone induces upregulation of the antioxidant transcription factor Nrf2 in ARPE-19 cells. Read More

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June 2018
2 Reads

Assessment of Genotoxic Effects by Constructing a 3D Cellular System with Highly Sensitive Mutagenic Human-Hamster Hybrid Cells.

Chem Res Toxicol 2018 Jun 19. Epub 2018 Jun 19.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science , Chinese Academy of Sciences , Hefei , Anhui 230031 , China.

Owing to complex microenvironmental conditions, it is challenging to reflect the actual biological responses of tissues or the body in a two-dimensional (2D) cellular system. In the present study, a low-attachment-cultivation technique was employed to establish a highly sensitive 3D human-hamster hybrid (A) model to study the mutagenic effects of environmental pollutants. The results showed that the established 3D system has apparent organizational characteristics. Read More

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June 2018
2 Reads

Maternal E-Cigarette Exposure Results in Cognitive and Epigenetic Alterations in Offspring in a Mouse Model.

Chem Res Toxicol 2018 Jun 15. Epub 2018 Jun 15.

School of Life Sciences, Faculty of Science , University of Technology Sydney , Sydney , New South Wales , Australia.

Electronic cigarette (e-cigarette) use is on the rise worldwide and is particularly attractive to young people and as a smoking substitute by pregnant woman. There is a perception in pregnant women and women of child-bearing age that the use of e-cigarettes (vaping) is safer than smoking tobacco cigarettes during pregnancy. However, there is little evidence to support this perception. Read More

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June 2018
4 Reads

Simple Determination of Gaseous and Particulate Compounds Generated from Heated Tobacco Products.

Chem Res Toxicol 2018 Jun 19. Epub 2018 Jun 19.

Department of Environmental Health , National Institute of Public Health , 2-3-6, Minami , Wako-shi , Saitama 351-0197 , Japan.

As a new form of cigarettes, heated tobacco products (HTPs) have been rapidly distributed worldwide. In this study, an improved method for analyzing gaseous and particulate compounds generated from HTPs is described. Smoke is collected using a GF-CX572 sorbent cartridge with 300 mg of carbon molecular sieves, that is, Carboxen 572 (CX572), and a 9 mm glass-fiber filter (GF). Read More

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June 2018
1 Read

Detoxification of Trimethylamine N-Oxide by the Mitochondrial Amidoxime Reducing Component mARC.

Chem Res Toxicol 2018 Jun 1;31(6):447-453. Epub 2018 Jun 1.

Department of Pharmaceutical and Medicinal Chemistry , Pharmaceutical Institute of the Christian-Albrechts-University of Kiel , 24118 Kiel , Germany.

Although known for years, the toxic effects of trimethylamine N-oxide (TMAO), a physiological metabolite, were just recently discovered and are currently under investigation. It is known that elevated TMAO plasma levels correlate with an elevated risk for cardiovascular disease (CVD). Even though there is a general consensus about the existence of a causal relationship between TMAO and CVD, the underlying mechanisms are not fully understood. Read More

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June 2018
1 Read

Pyrrolizidine Alkaloid Secondary Pyrrolic Metabolites Construct Multiple Activation Pathways Leading to DNA Adduct Formation and Potential Liver Tumor Initiation.

Chem Res Toxicol 2018 Jun 13. Epub 2018 Jun 13.

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

Pyrrolizidine alkaloids (PAs) and their N-oxide derivatives are hepatotoxic, genotoxic, and carcinogenic phytochemicals. PAs induce liver tumors through a general genotoxic mechanism mediated by a set of four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-derived DNA adducts. To date, the primary pyrrolic metabolites dehydro-PAs, their hydrolyzed metabolite DHP, and two secondary pyrrolic metabolites 7-glutathione-DHP (7-GS-DHP) and 7-cysteine-DHP are the known metabolites that can generate these DHP-DNA adducts in vivo and/or in PA-treated cells. Read More

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June 2018
4 Reads

Cytochromes P450 1A2 and 3A4 Catalyze the Metabolic Activation of Sunitinib.

Chem Res Toxicol 2018 Jun 18. Epub 2018 Jun 18.

Department of Pharmaceutical Sciences , Lipscomb University College of Pharmacy and Health Sciences , Nashville , Tennessee 37204-3951 , United States.

Sunitinib is a multitargeted tyrosine kinase inhibitor associated with idiosyncratic hepatotoxicity. The mechanisms of this toxicity are unknown. We hypothesized that sunitinib undergoes metabolic activation to form chemically reactive, potentially toxic metabolites which may contribute to development of sunitinib-induced hepatotoxicity. Read More

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June 2018
1 Read

Vector Control and Insecticidal Resistance in the African Malaria Mosquito Anopheles gambiae.

Chem Res Toxicol 2018 Jun 15. Epub 2018 Jun 15.

Biomedical Research Centre , University Hospital Hradec Kralove , Sokolska 581 , 500 05 Hradec Kralove , Czech Republic.

Mosquito-borne diseases (including malaria) belong among the leading causes of death in humans. Vector control is a crucial part of the global strategy for management of mosquito-associated diseases, when insecticide use is the most important component in this effort. However, drug and insecticide resistance threaten the successes made with existing methods. Read More

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June 2018
1 Read

Modeling of Human Hepatic and Gastrointestinal Ethanol Metabolism With Kinetic Mechanism-Based Full Rate Equations of the Component Alcohol Dehydrogenase Isozymes and Allozymes.

Chem Res Toxicol 2018 May 31. Epub 2018 May 31.

Alcohol dehydrogenase (ADH) is the principal enzyme responsible for metabolism of ethanol. Human ADH constitutes a complex family of isozymes and allozymes with striking variation in kinetic properties and tissue distribution. Liver and gastrointestinal tract are the major sites for first-pass metabolism (FPM). Read More

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May 2018
2 Reads

Camptothecin Efficacy to Poison Top1 Is Altered by Bisphenol A in Mouse Embryonic Fibroblasts.

Chem Res Toxicol 2018 Jun 5;31(6):510-519. Epub 2018 Jun 5.

Department of Oncologic Sciences , University of South Alabama Mitchell Cancer Institute , 1660 Spring Hill Avenue , Mobile , Alabama 36604 , United States.

Bisphenol A (BPA) is used heavily in the production of polycarbonate plastics, thermal receipt paper, and epoxies. Ubiquitous exposure to BPA has been linked to obesity, diabetes, and breast and reproductive system cancers. Resistance to chemotherapeutic agents has also been shown in cancer cell models. Read More

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June 2018
1 Read

Association of Type 2 Diabetes with Submicron Titanium Dioxide Crystals in the Pancreas.

Chem Res Toxicol 2018 Jun 5;31(6):506-509. Epub 2018 Jun 5.

Pigment-grade titanium dioxide (TiO) of 200-300 nm particle diameter is the most widely used submicron-sized particle material. Inhaled and ingested TiO particles enter the bloodstream, are phagocytized by macrophages and neutrophils, are inflammatory, and activate the NLRP3 inflammasome. In this pilot study of 11 pancreatic specimens, 8 of the type 2 diabetic pancreas and 3 of the nondiabetic pancreas, we show that particles comprising 110 ± 70 nm average diameter TiO monocrystals abound in the type 2 diabetic pancreas, but not in the nondiabetic pancreas. Read More

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June 2018
1 Read

Free-Base Nicotine Determination in Electronic Cigarette Liquids by H NMR Spectroscopy.

Chem Res Toxicol 2018 Jun 23;31(6):431-434. Epub 2018 May 23.

E-liquids usually contain significant nicotine, which will exist primarily in two forms, monoprotonated and free-base, the proportions of which are alterable through the effective pH of the medium. The fraction of nicotine in the free-base form is α, with 0 ≤ α ≤ 1. When dosed via aerosol, the two nicotine forms have different mechanisms and kinetics of delivery, as well as differing implications for harshness of the inhaled aerosol, so α is relevant regarding abuse liability. Read More

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June 2018
3 Reads

Mass Spectral Detection of Diethoxyphospho-Tyrosine Adducts on Proteins from HEK293 Cells Using Monoclonal Antibody depY for Enrichment.

Chem Res Toxicol 2018 Jun 6;31(6):520-530. Epub 2018 Jun 6.

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

Chronic illness from exposure to organophosphorus toxicants is hypothesized to involve modification of unknown proteins. Tyrosine in proteins that have no active site serine readily reacts with organophosphorus toxicants. We developed a monoclonal antibody, depY, that specifically recognizes diethoxyphospho-tyrosine in proteins and peptides, independent of the surrounding amino acid sequence. Read More

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June 2018
2 Reads

Low-Dose Arsenic Trioxide Modulates the Differentiation of Mouse Embryonic Stem Cells.

Chem Res Toxicol 2018 Jun 24;31(6):472-481. Epub 2018 May 24.

Department of Biotechnology, School of Life Science and Technology , Jinan University , Guangzhou 510632 , Guangdong Province , China.

Arsenic (As) is a well-known environmental pollutant, while arsenic trioxide (ATO) has been proven to be an effective treatment for acute promyelocytic leukemia, however, the mechanism underlying its dual effects is not fully understood. Embryonic stem cells (ESCs) exhibit properties of stemness and serve as a popular model to investigate epigenetic modifiers including environmental pollutants. Herein, the effects of low-dose ATO on differentiation were evaluated in vitro using a mouse ESCs (mESCs) cell line, CGR8. Read More

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June 2018
2 Reads

Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities.

Chem Res Toxicol 2018 Jun 23;31(6):435-446. Epub 2018 May 23.

Faculty of Pharmacy in Hradec Králové , Charles University , Akademika Heyrovského 1203 , 500 05 Hradec Králové , Czech Republic.

Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Read More

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June 2018
3 Reads

Systematic Approach to Organizing Structural Alerts for Reactive Metabolite Formation from Potential Drugs.

Chem Res Toxicol 2018 Jun 21;31(6):389-411. Epub 2018 May 21.

Awametox AB , Lilldalsvägen 17 A , SE-14461 Rönninge , Sweden.

Reactive metabolites are widely accepted as playing a pivotal role in causing idiosyncratic adverse drug reactions (IDR). However, much is unknown about the biological mechanisms of IDR, although the initiating event in most cases is an attachment of a reactive intermediate to macromolecules leading to immune-mediated responses. Reactive metabolites are also involved in many mutagenesis/carcinogenesis events by reacting with DNA. Read More

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June 2018
2 Reads

Exposure to Vinyl Chloride and Its Influence on Western Diet-Induced Cardiac Remodeling.

Chem Res Toxicol 2018 Jun 10;31(6):482-493. Epub 2018 May 10.

The Center of Cardiovascular Disorders , The First Hospital of the Jilin University , Changchun 130021 , China.

Obesity, usually caused by high fat diets (HFD), is a major public health issue worldwide, causing obesity associated cardiomyopathy. Moreover, the environmental toxicant vinyl chloride (VC) can exacerbate HFD-induced fatty liver disease. However, whether VC serves to enhance obesity-associated cardiomyopathy remains unclear. Read More

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June 2018
2 Reads
3.53 Impact Factor

Cigarette Filter Ventilation and Smoking Protocol Influence Aldehyde Smoke Yields.

Chem Res Toxicol 2018 Jun 17;31(6):462-471. Epub 2018 May 17.

Centre for Health Protection , National Institute for Public Health and the Environment (RIVM) , P.O. Box 1, 3720 BA Bilthoven , The Netherlands.

The WHO study group on tobacco product regulation (TobReg) advised regulating and lowering toxicant levels in cigarette smoke. Aldehydes are one of the chemical classes on the TobReg smoke toxicants priority list. To provide insight in factors determining aldehyde yields, the levels of 12 aldehydes in mainstream cigarette smoke of 11 Dutch brands were quantified. Read More

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June 2018
1 Read

Impact of Physicochemical Properties on Dose and Hepatotoxicity of Oral Drugs.

Authors:
Paul D Leeson

Chem Res Toxicol 2018 Jun 11;31(6):494-505. Epub 2018 May 11.

Paul Leeson Consulting Ltd , The Malt House, Main Street, Congerstone , Nuneaton, Warks CV13 6LZ , U.K.

A database containing maximum daily doses of 1841 marketed oral drugs was used to examine the influence of physicochemical properties on dose and hepatotoxicity (drug induced liver injury, DILI). Drugs in the highest ∼20% dose range had significantly reduced mean lipophilicity and molecular weight, increased fractional surface area, increased % of acids, and decreased % of bases versus drugs in the lower ∼60% dose range. Drugs in the ∼20-40% dose range had intermediate mean properties, similar to the mean values for the full drug set. Read More

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June 2018
2 Reads

Advancing Predictive Hepatotoxicity at the Intersection of Experimental, in Silico, and Artificial Intelligence Technologies.

Chem Res Toxicol 2018 Jun 10;31(6):412-430. Epub 2018 May 10.

Department of Chemical and Biological Engineering and Department of Biological Sciences Center for Biotechnology and Interdisciplinary Studies , Rensselaer Polytechnic Institute , Troy , New York 12180 , United States.

Adverse drug reactions, particularly those that result in drug-induced liver injury (DILI), are a major cause of drug failure in clinical trials and drug withdrawals. Hepatotoxicity-mediated drug attrition occurs despite substantial investments of time and money in developing cellular assays, animal models, and computational models to predict its occurrence in humans. Underperformance in predicting hepatotoxicity associated with drugs and drug candidates has been attributed to existing gaps in our understanding of the mechanisms involved in driving hepatic injury after these compounds perfuse and are metabolized by the liver. Read More

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June 2018
4 Reads

DNA Adduct Formation in the Lungs and Brain of Rats Exposed to Low Concentrations of [C]-Acetaldehyde.

Chem Res Toxicol 2018 May 9;31(5):332-339. Epub 2018 May 9.

Departamento de Bioquímica, Instituto de Química , Universidade de São Paulo , São Paulo , SP 05508-020 , Brazil.

Air pollution is a major environmental risk for human health. Acetaldehyde is present in tobacco smoke and vehicle exhaust. In this study, we show that [C]-acetaldehyde induces DNA modification with the formation of isotopically labeled 1, N-propano-2'-deoxyguanosine adducts in the brain and lungs of rats exposed to concentrations of acetaldehyde found in the atmosphere of megacities. Read More

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May 2018
3 Reads

Influence of Smoking Puff Parameters and Tobacco Varieties on Free Radicals Yields in Cigarette Mainstream Smoke.

Chem Res Toxicol 2018 May 7;31(5):325-331. Epub 2018 May 7.

Department of Food Science, College of Agricultural Sciences , Pennsylvania State University , University Park , Pennsylvania 16802 , United States.

Cigarette smoke is a major exogenous source of free radicals, and the resulting oxidative stress is one of the major causes of smoking-caused diseases. Yet, many of the factors that impact free radical delivery from cigarettes remain unclear. In this study, we machine-smoked cigarettes and measured the levels of gas- and particulate-phase radicals by electron paramagnetic resonance (EPR) spectroscopy using standardized smoking regimens (International Organization of Standardization (ISO) and Canadian Intense (CI)), puffing parameters, and tobacco blends. Read More

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May 2018
2 Reads

High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities.

Chem Res Toxicol 2018 May 4;31(5):308-318. Epub 2018 May 4.

Chemical Biology & Exposure Sciences, Biological Sciences Division , Pacific Northwest National Laboratory , Richland , Washington 99352 United States.

Cytochrome P450 monooxygenase (P450) enzymes metabolize critical endogenous chemicals and oxidize nearly all xenobiotics. Dysregulated P450 activities lead to altered capacity for drug metabolism and cellular stress. The effects of mixed exposures on P450 expression and activity are variable and elusive. Read More

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May 2018
4 Reads

In Vitro and in Vivo Studies of the Electrophilicity of Physcion and its Oxidative Metabolites.

Chem Res Toxicol 2018 May 2;31(5):340-349. Epub 2018 May 2.

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

Physcion (1,8-dihydroxy-3-methoxy-6-methyl-9,10-anthracenedione) is a bioactive component found in Polygoni Multiflori Radix (PMR), which has been widely used as traditional Chinese medicine. Unfortunately, studies showed hepatotoxicity of PMR during its clinical use. The mechanisms of its toxic action remain unknown. Read More

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May 2018
2 Reads

Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity.

Chem Res Toxicol 2018 May 30;31(5):291-301. Epub 2018 Apr 30.

Department of Pharmacology and Toxicology, Center for Human Toxicology , University of Utah , 30 South 2000 East, Room 201 Skaggs Hall , Salt Lake City , Utah 84112 , United States.

Wood/biomass smoke particulate materials (WBSPM) are pneumotoxic, but the mechanisms by which these materials affect lung cells are not fully understood. We previously identified transient receptor potential (TRP) ankyrin-1 as a sensor for electrophiles in WBSPM and hypothesized that other TRP channels expressed by lung cells might also be activated by WBSPM, contributing to pneumotoxicity. Screening TRP channel activation by WBSPM using calcium flux assays revealed TRPV3 activation by materials obtained from burning multiple types of wood under fixed conditions. Read More

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May 2018
2 Reads

Arsenite Targets the RING Finger Domain of Rbx1 E3 Ubiquitin Ligase to Inhibit Proteasome-Mediated Degradation of Nrf2.

Chem Res Toxicol 2018 May 23;31(5):380-387. Epub 2018 Apr 23.

Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response signaling pathway is a major mechanism for the cellular defense against oxidative stress. Arsenite, a widespread contaminant in drinking water, is known to induce oxidative stress and activate the Nrf2-dependent signaling pathway through the stabilization of the Nrf2 protein by inhibiting its ubiquitination via the Cul3-Rbx1-Keap1 (cullin 3, RING-box 1, and Kelch-like ECH-associated protein 1) E3 ubiquitin ligase, and its degradation by the 26S proteasome, though the underlying mechanism, remains elusive. In the present study, we demonstrated that arsenite could bind to the RING finger domain of Rbx1 in vitro and in cells, which led to the suppression of Cul3-Rbx1 E3 ubiquitin ligase activity, thereby impairing the Nrf2 ubiquitination and activating the Nrf2-induced antioxidant signaling pathway. Read More

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May 2018
7 Reads

Photosensitized Protein-Damaging Activity, Cytotoxicity, and Antitumor Effects of P(V)porphyrins Using Long-Wavelength Visible Light through Electron Transfer.

Chem Res Toxicol 2018 May 20;31(5):371-379. Epub 2018 Apr 20.

Department of General Systems Studies, Graduate School of Arts and Sciences , The University of Tokyo , Komaba 3-8-1 , Meguro-ku, Tokyo 153-8902 , Japan.

Photodynamic therapy (PDT) is a less-invasive treatment for cancer through the administration of less-toxic porphyrins and visible-light irradiation. Photosensitized damage of biomacromolecules through singlet oxygen (O) generation induces cancer cell death. However, a large quantity of porphyrin photosensitizer is required, and the treatment effect is restricted under a hypoxic cellular condition. Read More

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May 2018
2 Reads

Accurate Measurement of Formaldehyde-Induced DNA-Protein Cross-Links by High-Resolution Orbitrap Mass Spectrometry.

Chem Res Toxicol 2018 May 20;31(5):350-357. Epub 2018 Apr 20.

Department of Environmental Sciences and Engineering , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.

Genomic instability caused by DNA-protein cross-link (DPCs)-induced DNA damage is implicated in disease pathogenesis, aging, and cancer development. The covalent linkages between DNA and protein are induced by chemical reactions catalyzed by the endogenous metabolic intermediates and exogenous agents, such as aldehydes, chemotherapeutic agents, and ionizing radiation. Formaldehyde has been classified as a genotoxic carcinogen. Read More

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May 2018
4 Reads

Analysis and Identification of 2'-Deoxyadenosine-Derived Adducts in Lung and Liver DNA of F-344 Rats Treated with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol.

Chem Res Toxicol 2018 May 19;31(5):358-370. Epub 2018 Apr 19.

Masonic Cancer Center , University of Minnesota , 2231 Sixth Street SE , 2-210 CCRB, Minneapolis , Minnesota 55455 , United States.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are carcinogenic in animal models and are believed to play an important role in human lung carcinogenesis for cigarette smokers. Cytochrome P450-mediated metabolism of these tobacco-specific nitrosamines produces reactive species that alkylate DNA in the form of pyridyloxobutyl (POB)- or pyridylhydroxybutyl (PHB)-DNA adducts. Understanding the formation mechanism and overall levels of these adducts can potentially enhance cancer prevention methods through the identification of particularly susceptible smokers. Read More

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May 2018
6 Reads

Up-Regulation of T-Cell Activation MicroRNAs in Drug-Specific CD4 T-Cells from Hypersensitive Patients.

Chem Res Toxicol 2018 Jun 16;31(6):454-461. Epub 2018 May 16.

Instituto Politécnico Nacional , Unidad Profesional Interdisciplinaria de Biotecnología , Mexico City 07340 , México.

Dysregulation in the expression of microRNAs (miRNAs), single-stranded RNAs which regulate gene expression, has been associated with diseases such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), although their cellular origin has not been explored. Thus, the focus of this work was to study expression patterns of reported miRNAs involved in T-cell activation following drug-specific stimulation in peripheral blood mononuclear cells (PBMCs) and drug-specific CD4 T-cell clones (TCC) from patients with different cutaneous manifestations of delayed-type drug hypersensitivity reactions. CD4 T-cells from hypersensitive patients were stimulated to proliferate, secreted cytokines (IFN-γ and IL-22), cytolytic molecules (Granzyme B) and up-regulate miRNAs 24 to 48 h after drug exposure. Read More

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June 2018
4 Reads

Toxicokinetics in Risk Evaluations.

Authors:
Ans Punt

Chem Res Toxicol 2018 May 11;31(5):285-286. Epub 2018 Apr 11.

RIKILT Wageningen University and Research , P.O. Box 230 , 6700 AE Wageningen , The Netherlands.

Quantitative predictions of in vivo chemical levels based on in vitro data will become a cornerstone of next generation nonanimal risk evaluations. Both regulatory and scientific experience with quantitative toxicokinetics must increase now for this transition to happen. Read More

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May 2018
2 Reads

Reduction of Werner Syndrome Protein Enhances G:C → A:T Transition by O-Methylguanine in Human Cells.

Chem Res Toxicol 2018 May 12;31(5):319-324. Epub 2018 Apr 12.

Graduate School of Biomedical and Health Sciences , Hiroshima University , 1-2-3 Kasumi , Minami-ku, Hiroshima 734-8553 , Japan.

O-Methylguanine ( O-MeG) is a damaged base produced by methylating reagents. The Werner syndrome protein (WRN) is a cancer-related human DNA helicase. The effects of WRN reduction on O-MeG-caused mutagenesis were assessed by an siRNA-mediated knockdown in human U2OS cells, using a shuttle plasmid with a single O-MeG base in the supF gene. Read More

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May 2018
5 Reads

JQ-1 Inhibits Colon Cancer Proliferation via Suppressing Wnt/β-Catenin Signaling and miR-21.

Chem Res Toxicol 2018 May 11;31(5):302-307. Epub 2018 Apr 11.

Department of General Surgery , The Fourth Hospital Affiliated To Harbin Medical University , No. 37 Yiyuan Road , Harbin 150001 , China.

Bromodoamin and extraterminal (BET) protein inhibitors are a novel class of cancer therapeutics. Here we aim to investigate the efficacy and mechanism of JQ-1, a potent BET inhibitor, in colon cancer therapy. JQ-1 was used to treat SW480 colon cancer mouse xenografts. Read More

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May 2018
9 Reads

Accelerating the Pace of Chemical Risk Assessment.

Chem Res Toxicol 2018 May 6;31(5):287-290. Epub 2018 Apr 6.

Office of Research and Development , U.S. Environmental Protection Agency , Research Triangle Park , North Carolina 27711 , United States.

Changes in chemical regulations worldwide have increased the demand for new data on chemical safety. New approach methodologies (NAMs) are defined broadly here as including in silico approaches and in chemico and in vitro assays, as well as the inclusion of information from the exposure of chemicals in the context of hazard [European Chemicals Agency, " New Approach Methodologies in Regulatory Science ", 2016]. NAMs for toxicity testing, including alternatives to animal testing approaches, have shown promise to provide a large amount of data to fill information gaps in both hazard and exposure. Read More

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May 2018
3 Reads

β-Cyclodextrin Reverses Binding of Perfluorooctanoic Acid to Human Serum Albumin.

Chem Res Toxicol 2018 Apr 5;31(4):277-284. Epub 2018 Apr 5.

Department of Chemistry and Biochemistry , Florida International University , 11200 SW Eighth Street , Miami , Florida 33199 , United States.

Perfluorooctanoic acid (PFOA), a persistent organic pollutant known to cause adverse health effects, strongly binds to human serum albumin (HSA). β-Cyclodextrin (β-CD), a nontoxic cyclic sugar, strongly complexes PFOA in a host-guest complex and has been proposed for environmental remediation of PFOA. The interactions between HSA, PFOA, and β-CD were investigated in order to determine if β-CD can reverse the binding of PFOA to HSA, with potential therapeutic applications toward exposure to PFOA. Read More

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April 2018
4 Reads

Cigarillo and Little Cigar Mainstream Smoke Constituents from Replicated Human Smoking.

Chem Res Toxicol 2018 Apr 4;31(4):251-258. Epub 2018 Apr 4.

Battelle Memorial Institute, Public Health Center for Tobacco Research, 6115 Falls Road Suite 200 , Baltimore , Maryland 21209 , United States.

Little cigar and cigarillo smoking is increasing in popularity in the U.S., but little is known about the topography and mainstream smoke (MSS) constituents of these types of cigar products. Read More

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April 2018
2 Reads

Development of Polyclonal Antibodies for Detection of Diosbulbin B-Derived cis-Enedial Protein Adducts.

Chem Res Toxicol 2018 Apr 29;31(4):231-237. Epub 2018 Mar 29.

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

Diosbulbin B (DSB), a major component of herbal medicine Dioscorea bulbifera L. (DB), can be metabolized to an electrophilic intermediate, DSB-derived cis-enedial (DDE). DDE was suggested to contribute to the hepatotoxicity observed in experimental animals and humans after their exposure to DSB. Read More

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April 2018
8 Reads

Free Radical Production and Oxidative Stress in Lung Tissue of Patients Exposed to Sulfur Mustard: An Overview of Cellular and Molecular Mechanisms.

Chem Res Toxicol 2018 Apr 29;31(4):211-222. Epub 2018 Mar 29.

Chemical Injuries Research Center , System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences , 19945-581 Tehran , Iran.

Sulfur mustard (SM) is a chemical alkylating compound that primary targets lung tissue. It causes a wide variety of pathological effects in respiratory system such as chronic bronchitis, bronchiolitis obliterans, necrosis of the mucosa and inflammation, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. However, molecular and cellular mechanisms for these pathologies are still unclear. Read More

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April 2018
7 Reads

Role of Glucuronidation and P450 Oxidation in the Bioactivation of Bromfenac.

Chem Res Toxicol 2018 Apr 2;31(4):223-230. Epub 2018 Apr 2.

MyoKardia Inc , 333 Allerton Avenue , South San Francisco , California 94080 , United States.

Bromfenac is a nonsteroidal anti-inflammatory drug that was approved in the United States in 1997. It was withdrawn from clinical use less than one year later, in 1998, due to hepatotoxicity. We investigate the potential of bromfenac to be metabolized to reactive intermediates to further the current understanding of bromfenac bioactivation. Read More

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April 2018
4 Reads

Thiol Reactivity of Curcumin and Its Oxidation Products.

Chem Res Toxicol 2018 Apr 28;31(4):269-276. Epub 2018 Mar 28.

Department of Pharmacology, Division of Clinical Pharmacology, and Vanderbilt Institute of Chemical Biology , Vanderbilt University Medical School , Nashville , Tennessee 37232 , United States.

The polypharmacological effects of the turmeric compound curcumin may be partly mediated by covalent adduction to cellular protein. Covalent binding to small molecule and protein thiols is thought to occur through a Michael-type addition at the enone moiety of the heptadienedione chain connecting the two methoxyphenol rings of curcumin. Here we show that curcumin forms the predicted thiol-Michael adducts with three model thiols, glutathione, N-acetylcysteine, and β-mercaptoethanol. Read More

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April 2018
2 Reads

Relationship Between Fluoroquinolone Structure and Neurotoxicity Revealed by Zebrafish Neurobehavior.

Chem Res Toxicol 2018 Apr 27;31(4):238-250. Epub 2018 Mar 27.

Chinese Academy of Medical Sciences and Peking Union Medical College , 100730 Beijing , China.

Central nervous system side effects are one of the most frequently reported adverse reactions of fluoroquinolones (FQs). However, the mechanism is not fully understood. In this study, zebrafish ( Danio rerio) were used as a model system. Read More

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April 2018
4 Reads

The Double-Edged Sword Profile of Redox Signaling: Oxidative Events As Molecular Switches in the Balance between Cell Physiology and Cancer.

Chem Res Toxicol 2018 Apr 14;31(4):201-210. Epub 2018 Mar 14.

The intracellular redox state in the cell depends on the balance between the level of reactive oxygen species (ROS) and the activity of defensive systems including antioxidant enzymes. This balance is a dynamic process that can change in relation to many factors and/or stimuli induced within the cell. ROS production is derived from physiological metabolic events. Read More

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April 2018
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A Comparison of the Cyanide-Scavenging Capabilities of Some Cobalt-Containing Complexes in Mice.

Chem Res Toxicol 2018 Apr 14;31(4):259-268. Epub 2018 Mar 14.

Department of Environmental and Occupational Health, Graduate School of Public Health , The University of Pittsburgh , 100 Technology Drive , Pittsburgh , Pennsylvania 15219 , United States.

Four cobalt-containing macrocyclic compounds previously shown to ameliorate cyanide toxicity have been comparatively evaluated with an acute sublethal toxicity model in conscious (unanesthetized) adult male Swiss-Webster mice. All of the compounds (the cobalt-corrins cobalamin and cobinamide, a cobalt-porphyrin, plus a cobalt-Schiff base macrocycle) given 5 min prior to the toxicant dose significantly decreased the righting-recovery time of cyanide-intoxicated mice, but the doses required for maximal antidotal effect varied. Additionally, all of the compounds tested significantly reduced the righting-recovery time when administered at either 1 or 2 min after cyanide intoxication, but none of the compounds tested significantly reduced the righting-recovery time when delivered 5 min after the toxicant dose. Read More

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April 2018
3 Reads

Trans Lipid Library: Synthesis of Docosahexaenoic Acid (DHA) Monotrans Isomers and Regioisomer Identification in DHA-Containing Supplements.

Chem Res Toxicol 2018 Mar 6;31(3):191-200. Epub 2018 Mar 6.

ISOF, Consiglio Nazionale delle Ricerche , Via P. Gobetti 101 , 40129 Bologna , Italy.

Docosahexaenoic acid (DHA) is a semiessential polyunsaturated fatty acid (PUFA) for eukaryotic cells that is found in natural sources such as fish and algal oils and widely used as an ingredient for omega-3 containing foods or supplements. DHA effects are connected to its natural structure with six cis double bonds, but geometrical monotrans isomers can be formed during distillation or deodorization processes, as an unwanted event that alters molecular characteristics and annihilates health benefits. The characterization of the six monotrans DHA regioisomers is an open issue to address for analytical, biological, and nutraceutical applications. Read More

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March 2018
2 Reads

Influence of UGT2B10 Genotype on Urinary Excretion of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol- N-glucuronide by African American Smokers.

Chem Res Toxicol 2018 Mar 28;31(3):168-175. Epub 2018 Feb 28.

Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine , University of Southern California , Los Angeles , California 90089 , United States.

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

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March 2018
7 Reads

Who Are the New Editors of Chemical Research in Toxicology?

Authors:
Shana J Sturla

Chem Res Toxicol 2018 Feb;31(2):67

Department of Health Sciences and Technology, ETH Zurich , Schmelzbergstrasse 9, 8092 Zurich, Switzerland.

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February 2018
2 Reads