Michael S Denison

University of California, Davis | UCD · Department of Environmental Toxicology

Die Extraktion von Lipiden und lipophilen persistenten organischen Schadstoffen wie Dioxinen, dioxinähnlichen und nicht-dioxinähnlichen PCB aus Lebensmitteln tierischer Herkunft erfolgt in den Laboratorien der amtlichen Überwachung mit unterschiedlich effizienten Verfahren. Selbst dann, wenn Analyseergebnisse vorsorglich auf Frischgewicht basierend...

Aryl hydrocarbon receptor (AhR) activation by environmental agents and microbial metabolites is potentially implicated in a series of skin diseases. Hence, it would be very important to identify natural compounds that could inhibit the AhR activation by ligands of microbial origin as 6-formylindolo[3,2-b]carbazole (FICZ), indirubin (IND) and pityri...

Objective The biocompatibility of resin based dental composites has not yet been fully characterized even though certain monomers used in these composites are synthesized from Bisphenol A (BPA), a well-known estrogenic endocrine disruptor. As a result, they show structural relationship to BPA and can contain it as an impurity. Therefore, the estrog...

Air pollution poses a serious risk to human health. To help understand the contribution of smoke from wood burning to the harmfulness of air pollution toward the skin, we studied effects of liquid smoke, aqueous extracts of wood smoke condensate, a commercially available food flavor additive, in cultured keratinocytes. We report that liquid smoke c...

Exposure to volcanic ash is a long-standing health concern for people living near active volcanoes and in distal urban areas. During transport and deposition, ash is subjected to various physicochemical processes that may change its surface composition and, consequently, bioreactivity. One such process is the interaction with anthropogenic pollutan...

Diverse organic compounds, many derived from consumer products, are found in sewage sludge worldwide. Understanding which of these poses the most significant environmental threat following land application can be investigated through a variety of predictive and cell-based toxicological techniques. Nontargeted analysis using high-resolution mass spe...

In this study, an AhR-responsive reporter-gene cell-based bioassay CALUX was used to assess the biological potency of dioxins and dioxin-like PCBs (dl-PCBs) in top soil samples collected from a former airbase (A-So) and remote regions from urban and agricultural areas in Thua Thien Hue, Vietnam. In top soil collected from A-So airbase, Bioanalytica...

Background: Low maximum and action levels set by the European Union for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in pig meat (pork) have led to a demand for reliable and cost-effective bioanalytical screening methods implemented upstream of gas chromatog-raphy/high-resolution...

Urban wildfires may generate numerous unidentified chemicals of toxicity concern. Ash samples were collected from burned residences and from an undeveloped upwind reference site, following the Tubbs fire in Sonoma County, California. The solvent extracts of ash samples were analyzed using GC- and LC-high-resolution mass spectrometry (HRMS) and usin...

now published: https://www.researchgate.net/publication/350742630_Assessing_the_biological_reactivity_of_organic_compounds_on_volcanic_ash_implications_for_human_health_hazard AGU abstract: Volcanic ash eruptions may severely impact population living near an active volcano and in distal urban areas and are a cause of continuous health concern. Dur...

Background: Persistent organic pollutants (POPs) such as dioxins, dioxin-like chemicals and non-dioxin-like PCBs causing adverse effects to human health bio-accumulate through the food web due to their affinity for adipose tissues. Foods of animal origin are therefore the main contributors to human dietary exposure. The European Union’s (EU) food...

The aryl hydrocarbon receptor (AHR) plays pleiotropic roles in the development and physiology of vertebrates in conjunction with xenobiotic and endogenous ligands. It is best known for mediating the toxic effects of dioxin-like pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While most vertebrates possess at least one AHR that binds...

Polycyclic aromatic hydrocarbons (PAH) are a complex group of organic compounds, consisting of at least three fused aromatic rings, which are formed during combustion of organic matter. While some PAHs have been reported to have carcinogenic and/or mutagenic properties, another possible negative health impact is their endocrine disrupting potential...

1,2-naphthoquinone (1,2-NQ) and 1,4-naphthoquinone (1,4-NQ) are clinically promising biologically active chemicals that have been shown to stimulate the aryl hydrocarbon receptor (AhR) signaling pathway, but whether they are direct or indirect ligands or activate the AhR in a ligand-independent manner is unknown. Given the structural diversity of A...

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the biological and toxicological effects of an AhR lacking the entire PASB structurally diverse chemicals, including halogenated aromatic hydrocarbons. Ligand-dependent transformation of the AhR into its DNA binding form involves a ligand-dependent conforma...

The Ah receptor (AhR) is a ligand-dependent transcriptional factor that mediates the effects of structurally diverse chemicals. Ligand binding stimulates nuclear translocation of the AhR and leads to AhR DNA binding and increased gene expression. Studies of the molecular mechanisms by which ligands bind to and activate the AhR and AhR-dependent sig...

Organic aerosols generated from the smoldering combustion of wood critically impact air quality and health for billions of people worldwide; yet, the links between the chemical components and the optical or biological effects of woodsmoke aerosol (WSA) are still poorly understood. In this work, an untargeted analysis of the molecular composition of...

Malassezia furfur isolates from diseased skin preferentially biosynthesize compounds which are among the most active known Aryl-hydrocarbon Receptor (AhR) inducers, such as indirubin, tryptanthrin, indolo[3,2-b]carbazole and 6-formylindolo[3,2-b]carbazole. In our effort to study their production from Malassezia spp., we investigated the role of ind...

The aryl hydrocarbon receptor (AHR) plays pleiotropic roles in the development and physiology of vertebrates in conjunction with xenobiotic and endogenous ligands. It is best known for mediating the toxic effects of dioxin-like pollutants such as 2,3,7,8-tetracholordibenzo- p -dioxin (TCDD). While most vertebrates possess at least one AHR that bind...

Organic aerosols generated from the smoldering combustion of wood critically impact air quality and health for billions of people worldwide; yet, the links between the chemical components and the optical or biological effects of woodsmoke aerosols (WSA) are still poorly understood. In this work, an untargeted analysis of the molecular composition o...

The Ah receptor (AhR) is a ligand-dependent transcription factor belonging to the basic helix-loop-helix Per-Arnt-Sim (bHLH-PAS) superfamily. Binding to and activation of the AhR by a variety of chemicals results in the induction of expression of diverse genes and production of a broad spectrum of biological and toxic effects. The AhR also plays im...

Background In recent years, the BRAF inhibitor vemurafenib has been successfully established in the therapy of advanced melanoma. Despite its superior efficacy, the use of vemurafenib is limited by frequent inflammatory cutaneous adverse events that affect patients’ quality of life and may lead to dose reduction or even cessation of anti‐tumor ther...

Paperboard used as packaging, a non-inert material, can transfer chemicals into food. Over the years, endocrine disrupting compounds (EDCs), such as NonylPhenols (NPs), BisPhenol A (BPA) and phthalates have been shown to migrate from packaging materials into food. Due to chronic exposure and mixture effects of these EDCs, they could cause health ef...

BRAF inhibitors target the BRAF-V600E/K mutated kinase, the driver mutation found in 50% of cutaneous melanoma. They give unprecedented anti-tumor responses but acquisition of resistance ultimately limits their clinical benefit. The master regulators driving the expression of resistance-genes remain poorly understood. Here, we demonstrate that the...

Since 1987, the World Health Organization (WHO) carried out six global surveys on polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) and DDT in human milk, to identify global quantitative differences and provide time-trends. We applied a bioanalytical screening method designed for control of maximum levels (MLs)...

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that modulates gene expression following its binding and activation by structurally diverse chemicals. Species differences in AhR functionality have been observed, with the mouse AhR (mAhR) and human AhR (hAhR) exhibiting significant differences in ligand binding, coacti...

This international symposium provides an interdisciplinary forum for communicating scientific advances and emerging issues of concern to the environment and human health. Typically, 800-1000 delegates are expected, representing more than 800 abstracts presented in five parallel sessions. The program covers a broad range of core topics on analytical...

This international symposium provides an interdisciplinary forum for communicating scientific advances and emerging issues of concern to the environment and human health. Typically, 800-1000 delegates are expected, representing more than 800 abstracts presented in five parallel sessions. The program covers a broad range of core topics on analytical...

Commission Regulation (EU) 2017/644 of 5 April 2017 laying down methods of sampling and analysis for the control of levels of dioxins, dioxin-like PCBs and non-dioxin-like PCBs in certain foodstuffs and repealing Regulation (EU) No 589/2014. OJ L 92, 6.4.2017, p. 9–34

Commission Regulation (EU) 2017/771 of 3 May 2017 amending Regulation (EC) No 152/2009 as regards the methods for the determination of the levels of dioxins and polychlorinated biphenyls. OJ L 115, 4.5.2017, p. 22–42 (Feed)

Bioanalytical high-throughput and rapid screening methods for detection of dioxins and PCBs can reliably process up to 1.000 samples annually per technical assistant, reducing the workload of a GC/HRMS laboratory by up to 80 %. By sieving out contaminated samples suspected to exceed regulatory limits bioassays help to minimize instrument down time...

Within the scope of establishing strong EU-wide standards for routine methods, the Bioassay Research Laboratory at the EU-RL for Dioxins and PCBs in Feed and Food has upon request by the European Commission and in cooperation with the Department of Environmental Toxicology at the University of California Davis (US) evaluated and optimized the perfo...

Sensitive, efficient and high-throughput bioanalytical screening methods compliant with European Union (EU) legal requirements for the official control of the levels of dioxins and dioxin-like PCBs in food provide additional analytical capacities and reduce turnaround times and costs per sample. The authors describe concepts and procedures develope...

The Zenne River, crossing the Brussels region (Belgium) is an extremely urbanized river impacted by both domestic and industrial effluents. The objective of this study was to monitor the occurrence and activity of Endocrine Active Substances (EAS) in river water and sediments in the framework of the Environmental Quality Standards Directive (2008/1...

Patients with chronic kidney disease (CKD) are exposed to uremic toxins and have an increased risk of cardiovascular disease. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AHR). These toxins induce a vascular procoagulant phenotype. Here we investigated AHR activation in patients with...

Background: The Scheldt estuary is historically a highly polluted river system. While several studies have focused on contamination with metals, pesticides, Polycyclic Aromatic Hydrocarbons (PAHs) and marker PolyChlorinated Biphenyls (PCBs), no data are available concerning past contamination by dioxin-like compounds. Objectives: The objective o...

A novel type of diffusive gradients in thin-film (DGT) was combined with a chemically activated luciferase gene expression bioassay (CALUX) to measure estrogens in aquatic systems. The performance of this novel method was assessed with 17β-estradiol (E2) as the model steroid hormone, XAD 18 resin gel as the binding phase in the DGT method and VM7Lu...

In this study 42 polycyclic aromatic compounds (PACs) were investigated for their estrogenic potential using the VM7Luc4E2 transactivation assay (VM7Luc4E2-TA). Relative potencies (REPs) were determined for mass-balance analysis. In addition, compounds were tested in combination with the estrogen receptor (ER) antagonist ICI182,780 (ICI) and the Ah...

Background: Quaternary ammonium salts (QUATS), such as cetylpyridinium chloride (CPC) and benzalkonium chloride (BAK), are frequently used in antiseptic formulations, including toothpastes, mouthwashes, lozenges, throat and nasal sprays, and as biocides. Although in a recent ruling, the U.S. Food and Drug Administration (FDA) banned CPC from certa...

Laboratory safety requires protecting personnel from chemical exposures. Working with stock solutions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) in routine analysis of feed and food with bioanalytical or physicochemical methods raises some concerns. Since PCDD/PCDFs are considered as possibly acutely toxic, the potential ri...

Surface waters can contain a diverse range of organic pollutants, including pesticides, pharmaceuticals and industrial compounds. While bioassays have been used for water quality monitoring, there is limited knowledge regarding the effects of individual micropollutants and their relationship to the overall mixture effect in water samples. In this s...

The impact of unmonitored contaminants, also known as contaminants of emerging concern (CECs), on freshwater streams remains largely uncharacterized. Water samples from 31 streams representing urban, agricultural and undeveloped (i.e., open space) land use in Southern California (USA) were analyzed for in vitro and in vivo bioactivity. The extent a...

Commission Regulation (EU) 2017/771 of 3 May 2017 amending Regulation (EC) No 152/2009 as regards the methods for the determination of the levels of dioxins and polychlorinated biphenyls. OJ L 115, 4.5.2017, p. 22–42 (Feed)

Commission Regulation (EU) 2017/771 of 3 May 2017 amending Regulation (EC) No 152/2009 as regards the methods for the determination of the levels of dioxins and polychlorinated biphenyls. OJ L 115, 4.5.2017, p. 22–42 (Feed)

When compared to the European guidelines, PM10 (particulate matter up to 10-μm size) concentrations in Algeria are often exceeding the maximum limits, and in general, no information exists on the compounds bound on its surface. The objective of this study was to measure the dioxin-like activity of polychlorinated dibenzodioxines and dibenzofurans (...

Elucidation of the dimerization process of the aryl hydrocarbon receptor (AhR) with the AhR nuclear translocator (ARNT) is crucial for understanding the mechanisms underlying the functional activity of AhR, including mediation of the toxicity of environmental contaminants. In this work, for the first time a structural model of the AhR:ARNT dimer en...

Commission Regulation (EU) 2017/644 of 5 April 2017 laying down methods of sampling and analysis for the control of levels of dioxins, dioxin-like PCBs and non-dioxin-like PCBs in certain foodstuffs and repealing Regulation (EU) No 589/2014. OJ L 92, 6.4.2017, p. 9–34

Commission Regulation (EU) 2017/644 of 5 April 2017 laying down methods of sampling and analysis for the control of levels of dioxins, dioxin-like PCBs and non-dioxin-like PCBs in certain foodstuffs and repealing Regulation (EU) No 589/2014. OJ L 92, 6.4.2017, p. 9–34

Biosolids are a potentially valuable source of carbon and nutrients for agricultural soils; however, potential unintended impacts on human health and the environment must be considered. Virtually all biosolids contain trace amounts endocrine-disrupting chemicals derived from human use of pharmaceuticals and personal care products (PPCPs). One poten...

Ligand-dependent activation of the Ah receptor (AhR) can result in an extremely diverse spectrum of biological and toxic effects that occur in a ligand-, species- and tissue-specific manner. While the classical mechanism of AhR-dependent signal transduction is directly related to its ability to modulate gene expression, the dramatic diversity in re...

Inorganic arsenic is a human toxicant and carcinogen that has been extensively studied over decades; however, no definitive understanding for underlying mechanisms has been established. Arsenic is capable of modulating the expression of aryl hydrocarbon receptor (AhR)-regulated genes, nevertheless, whether its trivalent organic metabolites have sim...

The toxic effects of dioxins and related compounds (DRCs) are mediated by the aryl hydrocarbon receptor (AHR). Our previous study identified AHR1 and AHR2 genes from the red seabream (Pagrus major). Moreover, we found that AHR2 mRNA levels were notably elevated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in the early life stage of red se...

1,4-Dihydroxy-2-naphthoic acid (1,4-DHNA) is a bacterial-derived metabolite that binds the aryl hydrocarbon receptor (AhR) and exhibits anti-inflammatory activity in the gut. The structure-dependent AhR activity of hydroxyl/carboxy-substituted naphthoic acids was determined in young adult mouse colonic (YAMC) cells and human Caco2 colon cancer cell...

This presentation outlines procedures and results from initial validation and routine-QC performance evaluation of a new bioanalytical screening method for dioxins in pig’s meat, for which low MLs and ALs were set by EU legislation.

Cell-based bioanalytical screening methods (" bioassays ") have been effectively applied for a number of years in environmental and toxicological research laboratories and in laboratories for official control for monitoring of feed and food for elevated levels of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like PCBs...

Wood ash can be used as a fertilizer because it contains some important nutrients (K, Mg, Ca, P) as well as certain microelements such as Fe, Mn, Cu and Zn, and this in either pure form, in a pelleted version, or in combination with organic waste to form compost. It has been demonstrated that compost amended with (wood) ash (8-16%) provides better...

Today, there is international concern regarding the effects of natural and synthetic chemicals on the health of humans and wildlife since these emerging pollutants are able to interfere and act upon the hormonal system. These so-called endocrine-disrupting chemicals (EDCs) or endocrine active chemicals (EACs) are of particular concern to aquatic ec...

EPs (Emerging Pollutants) such as EDCs (Endocrine Disrupting Chemicals) are of special concern because they interfere with hormone biosynthesis, metabolism or action, resulting in a deviation from normal homeostatic control or reproduction. The European Commission added 15 chemicals to the watch list of the Environmental Quality Standards Directive...

Background Association of particulate matter with adverse health effects has been established in epidemiological studies and animal experiments. Epidemiological studies are difficult to undertake while animal studies are impractical for high-throughput toxicity testing. The ease and rapidity of in vitro tests emphasizes their potential for use in r...

Fishes in estuarine waters are frequently exposed to treated wastewater effluent, among numerous other sources of contaminants, yet the impacts of these anthropogenic chemicals are not well understood in these dynamic and important waterways. Inland silversides (Menidia beryllina) at an early stage of development [12 days posthatch (dph)] were expo...

Methyl-tert-butyl ether (MTBE) and its degradation by-product, tertiary butyl alcohol (TBA), are widespread contaminants detected frequently in groundwater in California. Since MTBE was used as a fuel-oxygenate for almost two decades, leaking underground fuel storage tanks are an important source of contamination. Gasoline components such as BTEX (...

The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in underst...

Structural superposition of the templates adopted. (A) PAS-A dimers, the reciprocal spatial orientation of the A’ α-helices is highlighted. (B) PAS-B dimers. (TIF)

Electrostatic Potential Surface (EPS) of the PAS-A dimers, comparison between models and templates. In each panel, the individual domains constituting the dimers are rotated each other of 180 degree, to obtain a representation as an “open book”. The potential range is defined in kT/e units according to the DelPhi software. Only the region defining...

Gel retardation analysis. Mouse AhR and ARNT were separately synthesized in vitro using TNT lysate, transformed in the presence of 20 nM TCDD or solvent control DMSO (1% v/v) and analyzed for DNA binding with the EMSA assay. Where indicated, 400 ng of anti-AhR antibody (M20), anti-ARNT antibody (N19) or corresponding IgG control (all antibodies and...

Sequence identity and similarity between the dimer models and the templates adopted. (PDF)

Hot spot list from PAS-A dimer templates, with related scores from the PPI prediction tools herein adopted (PDF)

Rank Products profile for the PAS-A dimer models. (PDF)

Hot spot list from PAS-B dimer templates, with related scores from the PPI prediction tools herein adopted (PDF)

Overall quality indices of the modeled structures. (PDF)

Rank Products profile for the PAS-A dimer models. (PDF)

The canonical fold of a PAS domain. In red are depicted the α-helices, in yellow the β-strands, in green those connecting loops whose length differs between the PAS-A and PAS-B domains (for such loops no structural information is available from the crystallographic templates of the PAS-A domains). The SS elements are labeled according to the nomenc...

Distance dependent statistical potential (DOPE) profiles. The protomer models of PAS-A domains (blue lines) are compared with the corresponding templates adopted (red lines). The green boxes highlight those regions that are not experimentally resolved in the structure of the template. (TIF)

Energy Decomposition analysis and Rank Products algorithm. (PDF)

Sequence alignments between the murine AhR/ARNT PAS domains and the templates chosen. The lower case gray shaded residues highlight the regions that needed a refinement during modeling. The heading bars depict the secondary structure assignment according to PSIPRED prediction for the target sequence (mAhR/ARNT) or DSSPcont attribution over the stru...

Distribution of the Z-score, calculated with ProSA. The distribution is represented along the sequence lengths taken from a dataset of experimentally resolved 3D protein structures. All of the models presented in this work (represented as black, yellow, green and red dots) fall into such distribution. (TIF)