Toxicology Commons^™

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 Departmental Research

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.

Organizational Effects Of Defeminizing Toxicants: Lessons Learned From An Environmental Sentinel Organism, The Fathead Minnow., Jonathan Ali

Theses & Dissertations

Endocrine disrupting compounds (EDCs) are chemicals that interfere with hormone function and are increasingly detected in aquatic environments, where they elicit adverse effects from exposed organisms. The toxicological effects of EDCs can be described as either activational (reversible) or organizational (irreversible), where the latter are associated with adverse outcomes in reproductive performance of adult fish. However, few studies have investigated the organizational impacts of anti-estrogenic or “defeminizing” EDCs, e.g. agrichemicals or pharmacological agents, in an environmentally-relevant or “sentinel” species. The objective of this study was to investigate the impacts of early-life EDC-initiated changes in estrogenic gene expression on organizational effects …

Effects Of Crude Oil On Tumor Suppressor P53 Polymorphisms In Laboratory-Exposed Atlantic Killifish, Fundulus Heteroclitus, Allison Margaret Nadler

Seton Hall University Dissertations and Theses (ETDs)

Polycyclic aromatic hydrocarbons (PAHs), constituents of crude oil, are implicated as a potent source of adverse toxicological effects on living organisms. To model the effects of PAHs in response to environmental oil spill disasters a species of killifish (Fundulus heteroclitus) was captured and exposed to crude oil in a laboratory-controlled setting. Over a period of 7 days, fish were dosed with crude oil by gavage, culled, and organs were harvested for analysis. Excitation-emission matrix spectroscopy (EEMS) of gall bladder tissue homogenates was used to verify exposure. Effects of PAHs on the p53 gene were evaluated as an indicator …

Identification And Quantification Of Cyanide And Its Metabolites In Lemur Urine, Jeremy Peralta

Student Theses

Cyanide is a chemical compound that contains the monovalent groups of carbon and nitrogen. This substance is considered a rapidly acting deadly chemical. However, some animals such as lemurs consume food products that are known to contain elevated levels of cyanide without major consequences. The mechanism by which the lemur can handle this high exposure to cyanide is unknown. In this study, we developed and validated two analytical methods for the determination of cyanide and two metabolites, thiocyanate and 2-aminothiazoline-4-carboxylic acid (ATCA) in lemur urine. The method was applied to 47 authentic lemur urine samples collected from 4 different species …

Age-Related Host Factors Regulate Lung Cancer Progression., John Caleb Greenwell

Electronic Theses and Dissertations

Cancer is largely a disease of the elderly. In the United States alone, 87% of all cancers in 2017 will be diagnosed in individuals aged 50 years or older. Among them, lung cancer is the deadliest, accounting for 1 in 4 cancer deaths. The 5-year survival rate is below 20%, a number which has not changed substantially over the past several decades. This underscores a desperate need for new strategies in prevention, early detection and treatment of this deadly disease. While tobacco use is unquestionably the number one risk factor for the development of lung cancer, the majority of diagnoses …

Toxicity And Mitochondrial Delivery Of Flavonol-Based Carbon Monoxide-Releasing Molecules, Hector Jose Esquer Heredia

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Despite the reputation of carbon monoxide (CO) as a silent killer, new evidence suggests that this gaseous molecule has anti-inflammatory, anti-cancer and vasoprotective properties. Unfortunately, little is known about the role of CO in the body. However, proteins present in mitochondria are believed to be important targets. We previously synthesized a class of novel and structurally modifiable flavonol-based CO-releasing molecules (CORMs). Flavonols are commonly found in fruits and vegetables. The base structure, Flav-1, is fluorescent, exhibits low toxicity, and releases CO after exposure to visible light. Previous reports indicate that addition of a triphenylphosphonium (TPP) tail allows chemical structures to …

Activation Des Éosinophiles Humains Par Des Nanoparticules, Denis Girard, Maxime Marion-Murphy

Rapports de recherche scientifique

L’économie du Canada, comme celle de bien d’autres pays industrialisés, bénéficie du développement des nanotechnologies dont le fort potentiel peut être exploité dans plusieurs secteurs industriels. Un nombre croissant d’entreprises québécoises de production de nanoparticules (NP) est d’ailleurs déjà implanté et tout porte à croire que d’autres emboîteront le pas dans les années à venir. Ce faisant, non seulement le nombre de travailleurs œuvrant dans la fabrication et la synthèse des NP augmentera sensiblement, mais également le nombre de ceux qui seront appelés à en manipuler et à en transformer dans les domaines des nanotechnologies en général. Une des conséquences …

A Historical Assessment Of Asbestos Exposure, Abatement Methods And Containment Efficacy During Asbestos Containing Material Removal Activities At A Large Federal Facility, Daniel A. Newfang

USF Tampa Graduate Theses and Dissertations

Asbestos sampling and monitoring data, starting from 2003, located in a large federal facility’s Asbestos Air Database Management (AADM) repository will be queried and analyzed on airborne asbestos fiber concentrations generated from abatement activities of asbestos-containing materials (ACM) and asbestos-containing building materials (ACBM). Historically, concerns expressed by personnel outside of the containment areas, whether adjacent to or quite a distance from the asbestos abatement activities present operational challenges for the project manager, potential angst and uneasiness to personnel residing next to the abatement activity as well as programmatic concerns to the building/facility managers. The concerned individuals working outside the abatement …

Multigeneration Effects Of Chronic Exposure To Polycyclic Aromatic Hydrocarbons In Gulf Killifish (Fundulus Grandis), Andrea Yammine

LSU Master's Theses

The goal of this study was to examine potential adaptation within two generations of Gulf killifish exposed to polycyclic aromatic hydrocarbons (PAH) while also investigating the use of mucus as an effective and non-lethal alternative to determine concentrations of 11-ketotestosterone (11-KT) and vitellogenin (VTG) of F. grandis. Multiple biomarkers were used to assess adaptation within these fish, such as lysozyme (enzyme critical in innate immunity), and 11-ketotestosterone and vitellogenin (endocrine hormones often affected by PAHs).

Mucal concentrations of 11-KT and VTG were determined and evaluated for effectiveness through comparative assays with blood plasma. This method was then applied to …

Effects Of Carboxylated Nanodiamonds On Macrophages During And After Differentiation, Maisoun E. Bani Hani

Biological Sciences Theses & Dissertations

Nanodiamonds (ND) are a carbon-based nanomaterial that are increasingly being proposed for developing novel imaging techniques, as carriers of biomolecules and therapeutic drugs, as coatings for implants, and for other biomedical applications. The exceptional chemical, mechanical, and optical properties of ND make this material suitable in a wide range of fields. The application of ND in the biomedical field is attractive but requires more in-depth investigation into the safety of ND and its interactions with different cells and systems. The effects of ND on the immune system are not fully understood or investigated and there are several controverting reports regarding …

Protective Effect Of Beta-Sitosterol Against Ethanol Toxemia, Dakota Cooper, April Boucher-Zamzo

Journal of Undergraduate Research at Minnesota State University, Mankato

Herbal medications have no indications of interactions with alcohol on their labels. There has been at least one clinical finding that saw palmetto with active ingredient beta-sitosterol used for enlarged male prostates caused pancreatic damage. This study with 20 male mice hypothesized that ethanol would increase the toxicity of beta-sitosterol. It was found that mice dosed by gavage with 0.1 ml of 95 proof ethanol died starting at the second dose and increased to 100% by the sixth dose (unexpected based on literature). 60-microgram injections of beta-sitosterol prevented deaths in 80% of the mice past the sixth dose opposite to …

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 Departmental Research

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.

Novel Insight Into The Liver-Lung Axis In Alcohol-Enhanced Acute Lung Injury., Lauren G. Poole

Electronic Theses and Dissertations

Background. Individuals who chronically abuse alcohol are almost 4 times more likely to develop Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), but the mechanisms by which alcohol abuse sensitizes the lung to injury are poorly understood. However, the lung appears to share many parallel mechanisms of injury with the liver- a primary target of alcohol abuse. The overarching goal of this dissertation was therefore to expand on established mechanisms of alcohol-induced liver injury to ask innovative questions about mechanisms of alcohol-enhanced acute lung injury, as well as to develop new tools that may …

The Comparative Cytotoxicity And Genotoxicity Of Hexavalent Chromium In Humans And Sea Turtles., Rachel M. Speer

Electronic Theses and Dissertations

Monitoring the health effects of environmental contaminants can be achieved using sentinel species as models. Leatherback sea turtles (Dermochelys coriacea) are an endangered marine species that may experience prolonged exposures to environmental contaminants including hexavalent chromium [Cr(VI)]. While Cr(VI) has been identified as a known human carcinogen, the health effects in marine species are poorly understood. In this study the cytotoxic and genotoxic effects of particulate and soluble Cr(VI) were assessed in leatherback lung cells and compared to those in human lung cells. Cr(VI) induced a concentration-dependent increase in cytotoxicity and genotoxicity in leatherback lung cells indicating Cr(VI) …

Enemy Exacerbation: Effects Of Predator Stress On Sulfate Lethality In Freshwater Amphipods (Gammarus Minus), Trevor Chapman

Electronic Theses and Dissertations

Predator cues can influence how aquatic organisms respond to anthropogenic contaminants. This study examined the effects of predator cues on behavior, metabolic rate, and sulfate (as Na₂SO₄) toxicity in amphipods (Gammarus minus). Predator cues included alarm cue (macerated conspecifics) and kairomone from mosquitofish (Gambusia affinis). Amphipods decreased activity and increased time in refuge when exposed to alarm cue, and increased time in refuge when exposed to kairomone. While median lethal concentrations (96-h LC₅₀) were not influenced by predator cues, analysis of dose response curves indicated that kairomone exposure increased amphipod …

Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre

Electronic Theses and Dissertations

Acute kidney injury (AKI), resulting from cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves cell death pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results indicate that cisplatin-treated mice had increased levels of ceramide and hexosylceramide. Pre-treatment of mice with inhibitors of ceramide synthesis prevented accumulation of ceramide and hexosylceramide in the renal cortex and attenuated cisplatin-induced AKI. To determine the role of ceramide metabolism to hexosylceramides in kidney injury, we treated mice with an inhibitor of glycosphingolipid synthesis. Inhibition of glycosphingolipid synthesis attenuated the accumulation of the hexosylceramide and exacerbated ceramide accumulation in the …

Distribution Of Polybrominated Diphenyl Ethers Among Demographic Categories, Giorvanni Merilis

USF Tampa Graduate Theses and Dissertations

Polybrominated Diphenyl Ethers (PBDEs) are flame retardants widely used within the United States in various products such as plastics, electronics, textiles and furniture. With an increase in production and usage, PBDEs have recently emerged as a contaminant of concern. Due to their chemical structure, PBDEs have the propensity to bioaccumulate in mammals. In fact, elevated PBDE concentrations have been recorded in human breast milk. Due to the potential widespread exposure to PBDEs, this study investigates human blood concentrations of PBDEs generated through the 2003-2004 National Health and Nutrition Examination Survey. Through the use of statistical modeling, a comparison of mean …

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 …

Characterizing The Impacts Of Contaminants On Fish Embryogenesis And Revealing An Alternate Molecular Mechanism Of Ahr Mediated Cardiac Defects, Corinna Singleman

Dissertations, Theses, and Capstone Projects

There is a long history of damage to natural ecosystems from environmental pollution. Many environmental contaminants are man-made and have been released with abandon over the last 100 years including dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and polychlorinated biphenyls (PCBs). These chemicals act on similar cellular processes and cause skin lesions, cancer, learning disabilities and reproductive problems in many vertebrates. There are many studies exploring various aspects of TCDD and PCB exposure on model and wild organisms. Few studies however, have compared effects of PCB mixtures on ecosystems to effects of individual PCBs in the lab. The first aim of this thesis is …