Toxicology Commons^™

Testing The Underlying Chemical Principles Of The Biotic Ligand Model (Blm) To Marine Copper Systems: Measuring Copper Speciation Using Fluorescence Quenching, Tara N. Tait, James C. Mcgeer, Scott Smith

Chemistry Faculty Publications

Speciation of copper in marine systems strongly influences the ability of copper to cause toxicity. Natural organic matter (NOM) contains many binding sites which provides a protective effect on copper toxicity. The purpose of this study was to characterize copper binding with NOM using fluorescence quenching techniques. Fluorescence quenching of NOM with copper was performed on nine sea water samples. The resulting stability con- stants and binding capacities were consistent with literature values of marine NOM, show- ing strong binding with log K values from 7.64 to 10.2 and binding capacities ranging from 15 to 3110 nmole mg C ^{−1 …}

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.

Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage. Similar cytoprotective effects were observed after transient shRNA-mediated silencing of Rps19, but not …

Rxtx And Micromedex, Shawn Hendrikx, Kelly Hatch

Western Libraries Publications

No abstract provided.

The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub

FIU Electronic Theses and Dissertations

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as …

Growth And Survival Of Salamanders Exposed To Different Formulations Of Glyphosate-Based Herbicide, Jessica Johnson

Mahurin Honors College Capstone Experience/Thesis Projects

Amphibian populations have been experiencing rapid declines worldwide in the past few decades. There are many proposed causations, including the use of agricultural chemicals such as herbicides. Glyphosate based herbicides are one of the most widely used herbicides. This study looks at the effects of different brands of glyphosate-based herbicides, including those intended for aquatic use, on the survival and growth of axolotl salamander larvae. Out of four brands of glyphosate herbicide (Aquamaster, Aquaneat, Helosate plus, and Roundup Pro), the survival rates of Roundup Pro were the lowest. Most mortality occurred between the 3 mg/L and 6 mg/L concentrations, during …

Stability Of Synthetic Cathinones In Oral Fluid Samples, Briana Miller, Jiyoung Kim, Marta Concheiro

Publications and Research

Synthetic cathinones are new stimulant drugs derived from cathinone that have been sold as “legal highs” worldwide. These compounds can elicit powerful effects such as delusions, hallucinations as well as other potentially dangerous behavior. New analogs with varying effects and potencies are constantly introduced in the market to evade legislation, and they are not detected by routine screening and confirmation methods. Oral fluid is an alternative matrix of increasing interest in forensic toxicology. Its collection is non-invasive and easily supervised, and positive drug findings typically reflect recent drug exposure. The focus of this research was to develop a method for …

Evaluation Of Perfluorohexane Sulfonate (Pfhxs) Exposure To Risk Of Liver Disease Caused By High Fat Fructose Diet, Dwight C. Anderson

Senior Honors Projects

Perfluorohexane sulfonate (PFHxS) has been used in products as surfactants[AS1] . These products include fluoropolymers and as protective and water-resistant coatings to different materials such as carpets, paper, and textiles. Also, evidence of PFHxS exposure has been reported in firefighters who use certain film forming foams. Current investigations have shown widespread exposure to PFHxS in the environment, specifically in drinking water. There has also been evidence of PFHxS accumulation in humans, with a half-life lasting several years.

PFHxS is one of several perfluoronated alkyl substances (PFAS). Other PFASs are considered to be hepatotoxic in rodents and potentially in humans. Studies …

Chronic Toxicity Of Binary‐Metal Mixtures Of Cadmium And Zinc To Daphnia Magna, Edgar Pérez, Tham C. Hoang

School of Environmental Sustainability: Faculty Publications and Other Works

The present study characterized the chronic effect of binary‐metal mixtures of cadmium (Cd) and zinc (Zn) on Daphnia magna. The titration design was chosen to characterize the 21‐d chronic effects of the binary‐metal mixtures on survival, growth, reproduction, and metal accumulation in D. magna. Using this design, increasing concentrations of Zn (10, 20, 40, 80, 120, 160, and 200 μg/L) were titrated against a constant concentration of 1.5 μg/L Cd. The results demonstrated that Cd was highly toxic to D. magna. In a mixture with Cd and Zn, sublethal concentrations of 10 and 20 μg/L Zn were …

Physiological Effects Of Five Different Marine Natural Organic Matters (Noms) And Three Different Metals (Cu, Pb, Zn) On Early Life Stages Of The Blue Mussel (Mytilus Galloprovincialis), Lygia Sega Nogueira, Adalto Bianchini, Scott Smith, Marianna Basso Jorge, Rachael L. Diamond, Chris M. Wood

Chemistry Faculty Publications

Metals are present in aquatic environments as a result of natural and anthropogenic inputs, and may induce toxicity to organisms. One of the main factors that influence this toxicity in fresh water is natural organic matter (NOM) but all NOMs are not the same in this regard. In sea water, possible protection by marine NOMs is not well understood. Thus, our study isolated marine NOMs by solid-phase extraction from five different sites and characterized them by excitation-emission fluorescence analysis—one inshore (terrigenous origin), two offshore (autochthonous origin), and two intermediate in composition (indicative of a mixed origin). The physiological effects of …

A Compromised Liver Alters Polychlorinated Biphenyl-Mediated Toxicity, Banrida Wahlang, Jordan T. Perkins, Michael C. Petriello, Jessie B. Hoffman, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the …

Kepone In The James River Estuary: Past, Current And Future Trends, Michael A. Unger, George G. Vadas

Reports

In late 1975, a manufacturing facility in Hopewell, VA had not only exposed workers to the chlorinated pesticide, Kepone, but had also severely contaminated the James River estuary. To assess the potential risk to the public, Virginia initiated a finfish-monitoring program in late 1975. Over the next 40 years over 13,000 samples were collected from the James River and Chesapeake Bay and analyzed for Kepone. Kepone production was eventually banned worldwide. The average Kepone concentrations found in most species began falling when the production of Kepone ended, but the averages remained over the action limit of 0.3 mgkg^-1 until …

An Open-Sourced Statistical Application For Identifying Complex Toxicological Interactions Of Environmental Pollutants, Jordan T. Perkins, Michael C. Petriello, Li Xu, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

The rising number of chemicals that humans are exposed to on a daily basis, as well as advances in biomonitoring and detection technologies have highlighted the diversity of individual exposure profiles (complex body burdens). To address this, the toxicological sciences have begun to shift away from examining toxic agents or stressors individually to focusing on more complex models with multiple agents or stressors present. Literature on interactions between chemicals is fairly limited in comparison with dose-response studies on individual toxicants, which is largely due to experimental and statistical challenges. Experimental designs capable of identifying these complex interactions are often avoided …

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings …

Immunotherapy Against Drugs Of Abuse, Gianna Raimondi (Class Of 2017)

Writing Across the Curriculum

Current treatments for drug addiction involve classical pharmacological therapy, involving the use of competitive or noncompetitive agonists (full, partial, or inverse) and antagonists. Drugs of abuse enter the brain after crossing the blood-brain barrier rapidly and binding to the proper receptor(s). They are able to do so because they are small and lipid soluble, and produce reinforcing effects by increasing levels of dopamine in brain areas associated with reward. This occurs in specific systems associated with addiction. In the mesolimbic system, neuron cell bodies originate in the ventral tegmental area (VTA) and project to the nucleus accumbens (NAc), amygdala, hippocampus, …

Aluminum And Phthalates In Calcium Gluconate: Contribution From Glass And Plastic Packaging, Robert A. Yokel, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

Introduction: Aluminum contamination of parenteral nutrition solutions has been documented for three decades. It can result in elevated blood, bone, and whole body aluminum levels associated with neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. The primary aluminum source among parenteral nutrition components is glass-packaged calcium gluconate, in which aluminum concentration the past three decades has averaged~ 4000 [mu]g/L, compared to < 200 [mu]g/L in plastic container-packaged calcium gluconate. A concern about plastic packaging is leaching of plasticizers, including phthalates, which have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity.

Methods: Aluminum was quantified in samples collected periodically over more than two years from three calcium gluconate sources used to prepare parenteral nutrition solutions; two packaged in glass (from France and the US) and one in plastic …

Bioanalysis For Cocaine, Opiates, Methadone And Amphetamines Exposure Detection During Pregnancy, Marta Concheiro, Elena Lendoiro, Ana De Castro, Eva Gonzalez-Colmenero, Ana Concheiro-Guisan, Patricia Penas-Silva, Manuel Macias-Cortina, Angelines Cruz-Landeira, Manuel Lopez-Rivadulla

Publications and Research

Drug exposure during pregnancy constitutes a major legal issue and public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography tandem mass spectrometry for the determination of cocaine, opioids, methadone and amphetamines, and compared the analytical results from the four different matrices. The cases were …

4-Methylcyclohexanemethanol Acute Toxicity To Daphnia And Its Effects On General Esterase And Glutathione S-Transferase Activity In Fathead Minnows, Rachel Clark, Jared Lewis, Jeehoon Jung, Benjamin Thornton

Research in Biology

In 2014, 10,000 gallons of crude MCHM spilled into the Elk River in West Virginia. Due to a paucity of information about the toxicity of this chemical prior to the spill, our research aimed to verify the published 48-h EC₅₀ for Daphnia magna (Daphnia) examine the effects of MCHM on two enzyme detoxification systems, general esterase and glutathione S-transferase, in Pimephales promelas (Fathead Minnow). We used pure MCHM instead of the crude form used in Eastman’s toxicity tests because the composition of crude MCHM is variable. The EC₅₀ we obtained for pure MCHM did not differ significantly from …

From Disposable Culture To Disposable People: Teaching About The Unintended Consequences Of Plastics, Sasha Adkins

Antioch University Full-Text Dissertations & Theses

Plastics, the epitome of disposable culture, pose both a toxicological and a spiritual problem. This dissertation examines plastics at a molecular level using the discourse of endocrine disruption, and at a sociological level using the discourses of eco-theology and environmental justice. Adding to the literature on the adsorption of toxicants to plastic marine debris, I demonstrate that certain types of plastic -- those containing mercaptans, such as styrene butadiene block copolymer -- efficiently concentrate methyl mercury from seawater. Further, samples of polycarbonate contributed mercury to seawater. I propose the term plastic-mediated magnification to describe the phenomenon that plastics, along with …