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Pharmacology, Toxicology and Environmental Health Commons™
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- Cytochrome P-450 (7)
- Mice as laboratory animals (3)
- Naphthalene (3)
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- Cytochrome P-450 Enzyme System (2)
- Cytochrome P450 (2)
- Gene expression (2)
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- Alkylation Repair Homolog 8 (1)
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Articles 1 - 15 of 15
Full-Text Articles in Pharmacology, Toxicology and Environmental Health
Epitranscriptomic Writer Systems And Codon Bias Regulate The Response To Environmental Stress, Andrea Leonardi
Epitranscriptomic Writer Systems And Codon Bias Regulate The Response To Environmental Stress, Andrea Leonardi
Legacy Theses & Dissertations (2009 - 2024)
Epitranscriptomic marks in the form of enzyme-catalyzed modifications to RNA nucleosides can be important regulators of translation and play integral roles in the response to stress. Dynamic changes in tRNA modification status can regulate the translation of stress response proteins whose transcripts have distinct codon biases. The epitranscriptomic writer Alkylation repair homolog 8 (ALKBH8) plays a crucial part in the translation of codon biased transcripts, as it regulates stop codon recoding, which is a specialized form of translation used to generate selenoproteins. ALKBH8 modifies the wobble uridine of selenocysteine tRNA (tRNASec) to promote the decoding of an internal UGA codon …
Biomarkers And Metabolic Mechanisms Of Tobacco Smoke-Induced Lung Disease, Matthew Alan Hartog
Biomarkers And Metabolic Mechanisms Of Tobacco Smoke-Induced Lung Disease, Matthew Alan Hartog
Legacy Theses & Dissertations (2009 - 2024)
The overall goal of the research conducted in this dissertation is to determine the role of cytochrome (CYP) P450-mediated xenobiotic bioactivation in the development of tobacco smoke-induced lung toxicity. The central hypothesis of this work is that CYP-mediated bioactivation of specific tobacco smoke constituents is an important contributor to the generation of tobacco smoke-induced lung inflammation and injury. The specific aims are 1) to demonstrate that CYP-mediated metabolism contributes to the onset of lung inflammation following tobacco smoke inhalation; 2) to demonstrate that specific tobacco smoke constituents undergo CYP-mediated bioactivation in vivo; 3) to demonstrate that CYP-mediated bioactivation of tobacco …
Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk
Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk
Legacy Theses & Dissertations (2009 - 2024)
Naphthalene (NA) is an omnipresent air pollutant and respiratory toxicant and a possible human lung carcinogen. NA induces cytotoxicity in airways following bioactivation by CYP (P450) enzymes. The overall goal of this study was to examine the relative contributions of hepatic and pulmonary CYPs to bioactivation, disposition and NA-induced pneumotoxicity in vivo. Substantial differences in the expression and enzymatic activity of P450s occur in various organs in human populations, which could modify susceptibility to NA-induced airway damage. The central hypothesis for this study was that NA has the potential to cause lung toxicity in humans and that the metabolism of …
Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal
Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal
Legacy Theses & Dissertations (2009 - 2024)
The use of silver nanoparticles (AgNPs) in a wide variety of consumer products (i.e. toothpastes, food containers, dietary supplements and garments) for their antimicrobial properties can lead to potential oral exposure in humans. To enhance their stability, AgNPs are coated with capping agents such as citrate and polyvinylpyrrolidone (PVP). Despite the lack of significant general toxicity based on hematology, blood chemistry and histology evaluations, the potential genotoxic effects of AgNPs cannot be ruled out and have to be addressed. Studies examining the genotoxic risks of AgNPs are needed because genotoxicity is a strong indicator of cancer risk. Here we examined …
Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho
Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho
Legacy Theses & Dissertations (2009 - 2024)
Expression of metabolic enzymes Cytochrome P450 (CYP) is highly affected by drugs, diseases, age and gender. The Intestinal microflora has been suggested to play a role in regulating CYP expression and antibiotic treatments would lead to changes in level and composition of microbiota in mouse gut. This study aims to analyze CYP expression changes in the liver and small intestine resulted from the reduction of intestinal microflora by antibiotics. Impacts on bile acid signaling were also analyzed for a better comprehension of the mechanisms involved in this modulation. Female C57BL/6J mice (9- to 13-week old) were treated with ampicillin (AMP) …
Consequences Of Developmental Lead (Pb2+) Exposure On Reproductive Strategies In Drosophila, Elizabeth Kathleen Peterson
Consequences Of Developmental Lead (Pb2+) Exposure On Reproductive Strategies In Drosophila, Elizabeth Kathleen Peterson
Legacy Theses & Dissertations (2009 - 2024)
Anthropogenic lead (Pb) pollution is ubiquitous in the environment and a risk factor for both human and wildlife health. Pb exposure has the potential to alter reproductive strategies with respect to mate choice and reproductive output. This could be especially deleterious if these changes disrupt adaptive behavioral and reproductive life history strategies. Therefore, the overall aim of this body of work was to examine the consequences of developmental Pb exposure on reproductive strategies, using Drosophila melanogaster as a model system. In all experiments, D. melanogaster were reared from egg stage to adulthood in either control or leaded medium and were …
Characterization Of Metallic And Semimetallic Oxide Nanoparticles In Industrial Wastewater And Associated Toxicity, Gary Roth
Legacy Theses & Dissertations (2009 - 2024)
Engineered nanomaterials (ENMs) play an increasing role in manufacturing and consumer products. Currently, there is no standard approach to studying ENM toxicity, and a growing body of literature suggests that ENMs may have toxicity differing from similar compounds in bulk or dissolved form. I examined ENMs used in the semiconductor manufacturing process called chemical-mechanical planarization (CMP) for their properties, removal in the wastewater treatment system (WWT), in-vitro toxicity, and location post-inhalation in-vivo. It was found that ENMs in CMP slurries have morphology determined by their elemental composition, but assessment of size and concentration can differ substantially between accepted techniques. Particles …
Study Of Protective Role Of Cytochrome P450s In Inflammatory Bowel Disease Using Cprlow Mouse Model, Xiaoyu Fan
Study Of Protective Role Of Cytochrome P450s In Inflammatory Bowel Disease Using Cprlow Mouse Model, Xiaoyu Fan
Legacy Theses & Dissertations (2009 - 2024)
Glucocorticoids (GCs) are potent regulatory factors for inflammation. The synthesis of GCs involves several cytochrome P450 enzymes, such as mitochondrial CYP11A1, CYP11B1, and microsomal CYP21. Previous studies have indicated that the GCs, including those released from adrenal glands, and those synthesized in extra-adrenal tissues, such as intestine, exert inhibitory effects on inflammatory bowel disease (IBD). In a previous study using an intestinal epithelium (IE)-specific P450 reductase (CPR) knockout (IE-Cpr-null) mouse model, the results suggested that the intestinal P450s had a protective role in DSS-induced acute colitis. In this study, using a hypomorphic CPR mouse model (Cprlow), which presents a global …
Role Of P450 Enzymes In Tobacco Dependence And Lung Tumorigenesis, Lei Li
Role Of P450 Enzymes In Tobacco Dependence And Lung Tumorigenesis, Lei Li
Legacy Theses & Dissertations (2009 - 2024)
The overall aim of this study is to better define the roles of P450 enzymes, particularly those in the CYP2A, 2B, and 2F gene subfamilies, in the metabolism and actions of tobacco-related chemicals. Tobacco smoke contains numerous compounds that are deleterious to health, including the primary addictive component nicotine and procarcinogenic compounds, such as naphthalene (NA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Our main hypotheses are i) that CYP2A and 2B enzymes are largely responsible for nicotine metabolism, and they can impact nicotine dependence; and ii) that CYP2A, 2B, and 2F enzymes play important and tissue-specific roles in NA and NNK bioactivation, leading …
Function And Regulation Of Intestinal P450 Enzymes : Insights From Conditional Cytochrome P450 Reductase Knockout Mouse Models, Yi Zhu
Legacy Theses & Dissertations (2009 - 2024)
The overall goal of this thesis work was to investigate the function and regulation of intestinal P450 enzymes (P450s). The central hypotheses are that 1) small intestinal (SI) P450s play an important role in the first-pass clearance of oral drugs and in bioactivation of chemicals that cause intestinal toxicity, 2) endogenous regulatory compounds produced by intestinal P450s are important for protection against chemical-induced colon inflammation, and 3) there is a cross talk between the liver and the SI that helps to maintain the overall xenobiotic-metabolism capacity of the digestive tract.
The Nasal Toxicity Of The Herbicide 2,6-Dichlorobenzonitrile : Mechanisms And Biomarkers, Fang Xie
The Nasal Toxicity Of The Herbicide 2,6-Dichlorobenzonitrile : Mechanisms And Biomarkers, Fang Xie
Legacy Theses & Dissertations (2009 - 2024)
The overall goal of this study is to investigate mechanisms of the potent nasal specific toxicity of the herbicide 2,6-dichlorobenzonitrile (DCBN) in rodents, and to determine whether DCBN could induce similar nasal toxicity in humans. The central hypotheses are 1) that the nasal specific toxicity of DCBN in rodents is mediated by its electrophilic intermediates that are formed through metabolic activation catalyzed by target tissue cytochrome P450 enzymes (P450) and can interfere with stem cell regeneration and differentiation in the olfactory epithelium (OE); and 2) that human nasal tissues are also capable of catalyzing bioactivation of DCBN. The specific aims …
Gene And Environment Interactions Modulate Immune System Influences On Social Behavior, Yubin Zhang
Gene And Environment Interactions Modulate Immune System Influences On Social Behavior, Yubin Zhang
Legacy Theses & Dissertations (2009 - 2024)
Autism is a neurodevelopmental disorder with unknown etiology, affecting about 1 in 110 children in the US. Here, we show that developmental exposure to anti-brain Abs impaired mouse social behaviors. BTBR mice, a mouse strain with high serum anti-brain Abs and behaviors that resemble autism, have more activated splenic B cells, CD4+ T cells (Th1, Th2 and Th17 subsets), and CD4+ T cells with expression of Vb6 chains than B6 mice (the control H-2 identical strain). Elevated numbers of activated (CD25+) CD4+Vb6+ cells also were detected in thymic preparations. All of the immunological and behavioral parameters of BTBR mice were …
Regulation Of The Aryl Hydrocarbon Receptor And The Signal Transducer And Activator Of Transcription 1 By Long-Term Estrogen Exposure In Breast Carcinoma Cells, Neal Englert
Legacy Theses & Dissertations (2009 - 2024)
The risk of developing breast cancer is known to be associated with a woman's lifetime exposure to estrogens, both endogenous and exogenous. Increased exposure to estrogens stimulates cellular proliferation, which is a widely accepted theory of estrogen receptor positive mammary carcinogenesis. The molecular mechanisms of gene expression regulation in response to long-term estrogen exposure (LTEE) of MCF-7 breast cancer cells were addressed in this study, with a focus on the aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 1 (STAT1).
Arsenic Speciation Analysis Of Biological Fluids : A Study Of Liquid Chromatography Coupled To Analytical Atomic Spectrometric Instrumentation, Kanna Ito
Legacy Theses & Dissertations (2009 - 2024)
Arsenic exists as many different chemical forms including inorganic, methylated and dietary species. The toxicity of these species varies: some are highly toxic and can cause adverse health effects in many parts of the body; others are considered relatively non-toxic. Monitoring arsenic exposure is usually accomplished by its direct measurement in biological fluids. Urine is the specimen of choice for assessing arsenic exposure, because of its short biological half-life in blood. There have been very few studies of arsenic species in blood, yet such research can provide valuable information on arsenic distribution and its metabolism in the body.
Genetic And Non-Genetic Factors That Cause Inter-Individual Variations In Cyp2a13 Gene Expression, Hong Wu
Genetic And Non-Genetic Factors That Cause Inter-Individual Variations In Cyp2a13 Gene Expression, Hong Wu
Legacy Theses & Dissertations (2009 - 2024)
The overall goal of this dissertation is to investigate the mechanisms underlying the large interindividual variations in susceptibility to lung carcinogenesis. We focused on CYP2A13, a respiratory tract-specifically expressed enzyme, which is the most efficient P450 towards bioactivation of a tobacco-related carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The expression level of CYP2A13 varies substantially among human lung samples. Our central hypothesis is that CYP2A13 expression level is affected by both genetic regulators and non-genetic factors. The specific aims are 1) to identify the mechanisms underlying the decreased allelic expression of a CYP2A13 allele (7520C>G); 2) to identify frequent single-nucleotide polymorphisms (SNPs), associated …