Toxicology Commons^™

Pfas Environmental Contamination In Central Maine, Megan H. Andersen

Honors Theses

PFAS (per- and polyfluoroalkyl substances) are toxic, persistent, and bioaccumulative chemicals that are used in a variety of consumer products and industrial applications. Paper mills across the state of Maine have used PFAS in their industrial paper making processes, and their wastes often flow for treatment into municipal sewage treatment facilities. PFAS contaminated municipal wastewater from the general use of PFAS consumer products are also processed by these plants. Liquid waste is condensed into solid waste septage and sludge, and in what was thought to be an environmentally friendly repurposing practice, municipal sludge and septage has been spread on plots …

Recyclage Primaire Des Matières Résiduelles Électroniques Au Québec : Portrait De La Santé Et De La Sécurité Du Travail Et Appréciation Du Risque Sanitaire, Sabrina Gravel, Bouchra Bakhiyi, Joseph Zayed, Sylvie Gravel, Daniel Côté, Brigitte Roberge, Jacques Lavoie, Loïc Wingert, France Labrèche

Rapports de recherche scientifique

En raison de l’utilisation croissante de composants et d’appareils électriques et électroniques, de même que de leur durée de vie relativement courte, la quantité de matières résiduelles électroniques ne cesse d’augmenter. Conséquemment, le nombre d’entreprises spécialisées dans le recyclage électronique (e-recyclage) est en nette croissance au Québec, comme ailleurs dans le monde. Ces entreprises emploient des travailleurs qui ont pour tâche de démonter les appareils afin d’en trier les composants qui seront subséquemment valorisés ou éliminés de manière sécuritaire. Ces tâches peuvent cependant entraîner l’exposition des travailleurs à un mélange de substances potentiellement toxiques, comprenant entre autres des poussières, des …

Determining The Effects Of Chemical Exposure On Hepatocyte Mitochondrial Networks And Cell Viability, Bethany Eaton

All Master's Theses

Mitochondria are cellular organelles that are becoming more recently studied. One of their main functions is the production of energy through cellular respiration, which is crucial to cell life. However, they are also associated with numerous disease states. It is hypothesized that reactive oxygen species (ROS), largely produced in mitochondria, induce oxidative stress and affect mitochondrial morphology along with cell viability. This study compares chemical exposure of menadione, an ROS producer, and phthalates (plasticizers) on two mouse hepatocyte cell lines to determine the effects they have on mitochondrial morphology and cell viability. Three experiments were performed to analyze the effects …

Behavioral Screening And Chiral Bioanalysis Of Emerging Stimulant-Type Drugs In Rats, Tyson R. Baird

Theses and Dissertations

The epidemic of drug use in the United States and elsewhere in the world has resulted in tragic loss of life and substantial economic costs. Novel psychoactive substances (NPS) are one of the contributors to this problem, and the lack of information about many of these drugs compounds their risk. This dissertation proposes a strategy to use intracranial self-stimulation (ICSS) as a behavioral screening tool to assess emerging drugs of abuse for their abuse potential in order to generate a proactive threat assessment. A series of stimulant-type drugs including methcathinone, α-pyrrolidinohexanophenone (α-PHP), cocaine, and the phenyltropane analogs of cocaine WIN35428 …

Formation, Antimicrobial Activity, And Biomedical Performance Of Plant-Based Nanoparticles: A Review, Ngoan Thi Thao Nguyen, Luan Minh Nguyen, Thuy Thi Thanh Nguyen, Thuong Thi Nguyen, Duyen Thi Cam Nguyen, Thuan Van Tran

Faculty, Staff and Student Publications

Because many engineered nanoparticles are toxic, there is a need for methods to fabricate safe nanoparticles such as plant-based nanoparticles. Indeed, plant extracts contain flavonoids, amino acids, proteins, polysaccharides, enzymes, polyphenols, steroids, and reducing sugars that facilitate the reduction, formation, and stabilization of nanoparticles. Moreover, synthesizing nanoparticles from plant extracts is fast, safe, and cost-effective because it does not consume much energy, and non-toxic derivatives are generated. These nanoparticles have diverse and unique properties of interest for applications in many fields. Here, we review the synthesis of metal/metal oxide nanoparticles with plant extracts. These nanoparticles display antibacterial, antifungal, anticancer, and …

Occurrence, Toxicity And Adsorptive Removal Of The Chloramphenicol Antibiotic In Water: A Review, Luan Minh Nguyen, Ngoan Thi Thao Nguyen, Thuy Thi Thanh Nguyen, Thuong Thi Nguyen, Duyen Thi Cam Nguyen, Thuan Van Tran

Faculty, Staff and Student Publications

Chloramphenicol is a broad-spectrum bacterial antibiotic used against conjunctivitis, meningitis, plague, cholera, and typhoid fever. As a consequence, chloramphenicol ends up polluting the aquatic environment, wastewater treatment plants, and hospital wastewaters, thus disrupting ecosystems and inducing microbial resistance. Here, we review the occurrence, toxicity, and removal of chloramphenicol with emphasis on adsorption techniques. We present the adsorption performance of adsorbents such as biochar, activated carbon, porous carbon, metal-organic framework, composites, zeolites, minerals, molecularly imprinted polymers, and multi-walled carbon nanotubes. The effect of dose, pH, temperature, initial concentration, and contact time is discussed. Adsorption is controlled by π-π interactions, donor-acceptor interactions, …

Development And Validation Of A Method For The Determination Of Designer Benzodiazepines In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc-Ms/Ms), Laura C. Defreitas

Student Theses

In recent years, new designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogues of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop ways to accurately test for these compounds in different biological matrices. This study focused to develop and validate a method for determining 17 new designer benzodiazepines in hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hair samples were decontaminated, pulverized, and 20 mg of the sample was incubated in …

A Study On The Efficacy Of A Naloxone Training Program, Gillian A. Beauchamp Md, Hoonani M. Cuadrado, Seth A. Campbell Pa-C, Bennie Eliason Chw, Chase Jones Do, Aaron Fedor Do, Lauren Grantz Pharmd, Csp, Paige Roth Lsw, Marna Greenberg

Department of Emergency Medicine

Introduction: The use of naloxone to reverse a potentially fatal opioid overdose is a harm reduction strategy that reduces mortality and increases the potential for referral to substance use treatment for affected individuals. In the setting of outreach performed by a street medicine team, we aimed to determine the effectiveness of an educational intervention involving distribution of naloxone accompanied by a brief instructive session about opioids, opioid overdose, and medication administration. Methods: Our street medicine outreach team distributed 200 naloxone kits to clinicians and volunteers involved in caring for patients on ‘street rounds,’ as well as in shelters, soup kitchens, …

Childhood Exposure To Per- And Polyfluoroalkyl Substances (Pfas) And Neurobehavioral Domains In Children At Age 8 Years, Ann M. Vuong, Kimberly Yolton, Changchun Xie, Kim N. Dietrich, Joseph M. Braun, Glenys M. Webster, Antonia M. Calafat, Bruce P. Lanphear, Aimin Chen

Environmental & Global Health Faculty Research

Background: Toxicological studies have raised concerns regarding the neurotoxic effects of per- and polyfluoroalkyl substances (PFAS). However, observational evidence from human studies investigating the association between childhood PFAS and neurobehavior is limited and remains unclear. Objectives: To examine whether childhood PFAS concentrations are associated with neurobehavior in children at age 8 years and whether child sex modifies this relationship. Methods: We used data from 208 mother-child dyads in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort (Cincinnati, OH, USA). We quantified PFAS in child serum at 3 and 8 years. We assessed …

Innate Immune Activation By Checkpoint Inhibition In Human Patient-Derived Lung Cancer Tissues, Teresa W. M. Fan, Richard M. Higashi, Huan Song, Saeed Daneshmandi, Angela L. Mahan, Matthew S. Purdom, Therese J. Bocklage, Thomas A. Pittman, Daheng He, Chi Wang, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Although Pembrolizumab-based immunotherapy has significantly improved lung cancer patient survival, many patients show variable efficacy and resistance development. A better understanding of the drug’s action is needed to improve patient outcomes. Functional heterogeneity of the tumor microenvironment (TME) is crucial to modulating drug resistance; understanding of individual patients’ TME that impacts drug response is hampered by lack of appropriate models. Lung organotypic tissue slice cultures (OTC) with patients’ native TME procured from primary and brain-metastasized (BM) non-small cell lung cancer (NSCLC) patients were treated with Pembrolizumab and/or beta-glucan (WGP, an innate immune activator). Metabolic tracing with ¹³C₆-Glc/ …

Developmental Ethanol Exposure Causes Central Nervous System Dysfunction And May Slow The Aging Process In A Drosophila Model Of Fetal Alcohol Spectrum Disorder, Khaoula Belhorma, Nahed Darwish, Elizabeth Benn-Hirsch, Annalisa Duenas, Hillary Gates, Navneet Sanghera, Jodie Wu, Rachael L. French

Faculty Research, Scholarly, and Creative Activity

Alcohol is a known teratogen, and developmental exposure to ethanol results in fetal alcohol spectrum disorder (FASD). Children born with FASD can exhibit a range of symptoms including low birth weight, microcephaly, and neurobehavioral problems. Treatment of patients with FASD is estimated to cost 4 billion dollars per year in the United States alone, and 2 million dollars per affected individual's lifetime. We have established Drosophila melanogaster as a model organism for the study of FASD. Here we report that mutations in Dementin (Dmtn), the Drosophila ortholog of the Alzheimer's disease-associated protein TMCC2, convey sensitivity to developmental ethanol exposure, …

Contemporary Brazilian Catholicism And Healing Practices: Notes On Environmentalism And Medicalization, Juliano F. Almeida

Journal of Global Catholicism

Anthropological studies on Brazilian Catholicism traditionally focused on popular variants of this religious practice and their relationship with the official Catholicism. Encouraged by recent anthropological perspectives, which highlight the relevance of devoting researches not only on the margins, but also on the center of social practices, this paper analyzes contemporary practices of Brazilian Catholic friars and priests on health promotion. The analysis of their publications (books that include practices and tips on health and that became best sellers etc.), as well as interviews, allows us to perceive a process of environmentalization on the contemporary Brazilian Catholicism. This process seems to …

Stress, Alcohol Use, And Punitive Parenting During The Covid-19 Pandemic, Jennifer Price Wolf, Bridget Freisthler, Caileigh Chadwick

Faculty Research, Scholarly, and Creative Activity

Background
Emerging research suggests that parents are experiencing heightened stress during the COVID-19 pandemic. Parental stress is a risk factor for harsh or punitive parenting, and this association may be exacerbated by the use of alcohol.
Objective
We examine whether parental stress is associated with use of punitive parenting, as well as whether this association is modified by drinking pattern.
Participants & setting
We used advertisements and word-of-mouth to recruit 342 parents living in Central Ohio during the initial stay-at-home order for COVID-19.
Methods
We used geographic ecological momentary assessment (gEMA) to measure parental stress and punitive parenting during three …

Development Of A Rapid Drug Detection Method For Insects Using Paper Spray Ionization Mass Spectrometry (Psi-Ms), Alexandria Plyler

Undergraduate Research and Scholarship Symposium

Insects have the ability to reflect the chemical environment that they have developed in. Thus, necrogenous insects can reflect the chemical environment of cadavers they have fed on. Forensic scientists can potentially utilize insect larvae as an alternate biological matrix to detect drugs in cadavers that are skeletonized, burned, or otherwise badly damaged. Analysis of insects using paper spray ionization mass spectrometry (PSI-MS), an analytical method requiring little to no sample preparation, could prove a rapid, cost-effective, and non-destructive alternative form of toxicological analysis. Traditional tissue analysis via GC and LC-MS often require lengthy sample preparation, use expensive reagents, and …

New Psychoactive Substances In Taiwan: The Current Situation And Initiative For Rational Scheduling, Wen-Jing Yu, Linda B. Cottler, Jih-Heng Li

Journal of Food and Drug Analysis

Use of New Psychoactive Substances (NPS) has posed a global threat to public health and the security of the population. As of December 2019, the NPS items identified in total have outnumbered by three to one the controlled substances listed in the 1961 and 1971 UN Drug Conventions. However, most of these NPS have not been scheduled by the United Nations because of their easy modification on the chemical structures to shun control. Currently, the scheduling and control of NPS is mostly at the national level and a rational scheduling of NPS by objective assessments is essential but often lacking. …

Impact D’Un Stress Thermique Représentatif Des Milieux De Travail Sur L’Absorption Pulmonaire Et La Toxicocinétique De Trois Solvants Organiques, Axelle Marchand, Pierre Brochu, Jessie Ménard, Sami Haddad

Rapports de recherche scientifique

Plusieurs des changements physiologiques associés à la thermorégulation peuvent influencer la cinétique des substances chimiques dans le corps humain, comme la ventilation alvéolaire et la redistribution du débit sanguin aux organes. Si certaines mesures préventives peuvent permettre de protéger les travailleurs contre les effets directs de la chaleur, elles ne permettent toutefois pas d’empêcher les processus de thermorégulation de prendre place. Une exposition concomitante à la chaleur et aux substances chimiques volatiles peut donc entraîner des variations dans l’absorption par inhalation et dans la cinétique de ces substances, biaisant ainsi l’évaluation des données de biosurveillance.

Dans cette étude, l’influence de …

Environmentally Marginalized Populations: The "Perfect Storm" For Infectious Disease Pandemics, Including Covid-19, Gabriella Y. Meltzer, Oyemwenosa Avenbuan, Christina Awada, Oluwakemi B. Oyetade, Tricia Blackman, Simona Kwon Drph, Mph, Esther Erdei Phd, Judith T. Zelikoff Phd

Journal of Health Disparities Research and Practice

COVID-19 has exacted a severe toll on the United States population’s physical and mental health and its effects have been felt most severely among people of color and low socioeconomic status. Using illustrative case studies, this commentary argues that in addition to COVID-19 health disparities created by psychosocial stressors such as the inability to socially distance and access quality healthcare, environmental justice communities have the additional burden of disproportionate exposure to toxic contaminants that contribute to their higher risk of COVID-19. Environmental contaminants including heavy metals and persistent organic pollutants found contaminating their nearby environments can alter the immune response, …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Improving The Accuracy Of Occupational Hygiene Models Used To Estimate Worker Exposure To Solvent Vapours, Spéro Abattan, Stéphane Hallé, Daniel Drolet, Ali Bahloul, Patrick Eddy Ryan, Wejden Chouchene, Carlos Castro Ruiz, Jérôme Lavoué, Maximilien Debia

Rapports de recherche scientifique

Chaque année, des travailleurs québécois subissent des effets sur leur santé après avoir été exposés à des substances chimiques, notamment à des solvants. La modélisation des expositions professionnelles occupe une place importante dans la prévention des risques. Cette recherche vise à étudier différents aspects de la modélisation pour estimer des expositions professionnelles à des vapeurs de solvants dans le but d’en améliorer la justesse de prédiction. Le travail de recherche a été effectué en deux volets. Grâce à la mise en œuvre de tests à petite échelle (volet I) et à échelle humaine (volet II), les travaux présentés dans cette …

Occupational Exposure To Antineoplastic Drugs: What About Hospital Sanitation Personnel?, France Labrèche, Capucine Ouellet, Brigitte Roberge, Nicolas J Caron, Ahmed Yennek, Jean-François Bussières

Études primaires

Objective

Occupational exposure to antineoplastic drugs (ANPs) occurs mainly through dermal contact. Our study was set up to assess the potential exposure of hospital sanitation (HS) personnel, for whom almost no data are available, through contamination of surfaces they regularly touch.

Methods

In the oncology departments of two hospitals around Montreal, surface wipe samples of 120–2000 cm² were taken at 10 sites cleaned by the HS personnel and five other sites frequently touched by nursing and pharmacy personnel. A few hand wipe samples were collected to explore skin contamination. Wipes were analyzed by ultra-performance liquid chromatography tandem–mass spectrometry for …

Maternal Engineered Nanomaterial Inhalation Exposure: Cardiac Molecular Reprogramming In Progeny Through Epigenetic And Epitranscriptomic Mechanisms, Amina Kunovac

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: Nano-titanium dioxide (TiO₂), a prominently utilized engineered nanomaterial (ENM), is being employed for its physiochemical properties in several fields including the food industry, manufacturing, and biomedicine. As the prevalence of this ENM, and other particulate matter grows, so does the concern for antagonistic consequences on long-term heart function in vulnerable populations, which until now have not been investigated. Due to the reliance of the heart on the ATP generating capacity of mitochondria for contraction, understanding the role of mitochondrial bioenergetics and structure is pivotal in understanding the repercussions of particulate matter exposure during gestation. As the mass …

In Vitro And In Vivo Toxicological Evaluation Of Emissions From The Fused Filament Fabrication Three-Dimensional Printing, Mariana T. Farcas

Graduate Theses, Dissertations, and Problem Reports (ETD)

Fused filament fabrication (FFF), a three-dimensional (3-D) printing process, is an emerging technology that has recently gained wide popularity among both consumers and manufacturers. As filament is heated to above its glass transition temperature in a 3-D printer, a portion may undergo thermal decompostion, which releases ultrafine particles (UFP) and volatile organic compounds (VOCs) with potential adverse respiratory health effects are released into the air. This study's central hypotheses is that emissions generated during 3-D printing are toxic and exposure to these emissions induces pulmonary and systemic adverse health effects. Considering that currently, limited understanding is available on the health …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Development And Characterization Of An Adaptable Aerosolized Methylene Diphenyl Diisocyanate Generation System, Simon Aubin, Loïc Wingert, Sébastien Gagné, Livain Breau, Jacques Lesage

Études primaires

Reactive semivolatile contaminants, such as isocyanates, can be particularly difficult to assess in occupational environments. While standard methods exist for isocyanates, there are still significant differences between the results they provide for various occupational environments or processes. This study presents the validation of a laboratory system for the generation of controlled atmospheres of isocyanates. A system consisting of different modules generated airborne methylene diphenyl diisocyanate (MDI) by nebulizing a solution into mixing and exposure chambers with control of flow rate, temperature, and relative humidity. Sampling was performed through an eight-port flow splitter that allowed only very slight within-test variability. MDI …

Physicochemical Characterization And Genotoxicity Of The Broad Class Of Carbon Nanotubes And Nanofibers Used Or Produced In Us Facilities, Kelly Fraser, Vamsi Kodali, Naveena Yanamala, M. Eileen Birch, Lorenzo Cena, Gary Casuccio, Kristin Bunker, Traci L. Lersch, Douglas E. Evans, Aleksandr Stefaniak, Mary Ann Hammer, Michael L. Kashon, Theresa Boots, Tracy Eye, John Hubczak, Sherri A. Friend, Matthew Dahm, Mary K. Schubauer-Berigan, Katelyn Siegrist, David Lowry, Alison K. Bauer, Linda M. Sargent, Aaron Erdely

Public Health Sciences Faculty Publications

Background Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine …

Eelgrass (Zostera Marina) Population Decline In Morro Bay, Ca: A Meta-Analysis Of Herbicide Application In San Luis Obispo County And Morro Bay Watershed, Tyler King Sinnott

Master's Theses

The endemic eelgrass (Zostera marina) community of Morro Bay Estuary, located on the central coast of California, has experienced an estimated decline of 95% in occupied area (reduction of 344 acres to 20 acres) from 2008 to 2017 for reasons that are not yet definitively clear. One possible driver of degradation that has yet to be investigated is the role of herbicides from agricultural fields in the watershed that feeds into the estuary. Thus, the primary research goal of this project was to better understand temporal and spatial trends of herbicide use within the context of San Luis …

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …

Discoveries In Aerosol Science: Characterization Of Nanoparticles Emitted From Metallic Coils In Electronic Cigarettes, Kaushal Prasad

The Journal of Purdue Undergraduate Research

Electronic (e-) cigarettes, also known as electronic nicotine delivery systems, are battery-operated devices that are growing in popularity worldwide. Although e-cigarettes are known to be safer than traditional cigarettes, their potential health risks have not been extensively reviewed yet. In this study, aerosol nanoparticles generated from e-cigarette heaters were characterized. Kanthal A1 (iron + chromium + aluminum) coils, without nicotine solution or a wick, were installed in an e-cigarette atomizer. The operating conditions were varied coil resistances (0.1–1.0 Ω), a set applied power (10 W), and a stable duty cycle (50%: 5 s on, 5 s off ). The size …

N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …