Medical Toxicology Commons^™

Mnsod And Autophagy In Prevention Of Oxidative Mitochondrial Injuries Induced By Uvb In Murine Skin, Vasudevan Bakthavatchalu

Theses and Dissertations--Toxicology and Cancer Biology

UVB radiation is a known environmental carcinogen that causes DNA damage and increase ROS generation in mitochondria. Accumulating evidence suggests that mtDNA damage and increased ROS generation trigger mitochondrial translocation of p53. Within mitochondria, p53 interacts with nucleoid macromolecular complexes such as mitochondrial antioxidant MnSOD, mitochondrial DNA polymerase Polγ, and mtDNA. Mitochondria are considered to be a potential source for damage-associated molecular patterns (DAMPs) such as mtDNA, cytochrome C, ATP, and formyl peptides. Intracytoplasmic release of DAMPs can trigger inflammasome formation and programmed cell death processes. Autophagic clearance of mitochondria with compromised integrity can inhibit inflammatory and cell death processes. …

Novel Mechanism Leading To Mismatch Repair Deficiency And Mutator Phenotype, Janice Ortega Rodríguez

Theses and Dissertations--Toxicology and Cancer Biology

DNA mismatch repair (MMR) is a critical genome-maintenance system. It ensures genome stability by correcting mismatches generated during DNA replication, suppressing homologous recombination, and inducing apoptosis in response to severe DNA damage. As a result, defects in MMR lead to genome-wide mutations and susceptibility to both hereditary and sporadic cancer syndromes. The hallmark of cancer cells defective in MMR is their ability to display frequent instability in simple repetitive DNA sequences, a phenomenon called microsatellite instability (MSI). However, only ~70% of the MSI-positive tumors have identifiable MMR gene mutations, indicating that additional factor(s) are responsible for the MSI phenotype in …

Physiological And Toxicological Roles Of Abc Transporters In Cellular Efflux Of Substrates, Donna J. Coy

Theses and Dissertations--Toxicology and Cancer Biology

ATP-binding cassette (ABC) transporters are transmembrane proteins that transport a wide variety of substrates across intra and extra-cellular membranes. A few examples of endo and xenobiotic substrates are metabolic products, lipids, sterols, and drugs. An important function of ABC transporters involved in export is to prevent intracellular the buildup of toxic products. Several ABC transporters have also been associated with drug resistance upon treatment with chemotherapeutic agents. P-glycoprotein (P-GP) and the multidrug resistant (MRP) transporters of the ABC C family are examples of transporters that confer chemo-resistance.

We have studied two unique roles of ABC transporters in the liver and …

In Vivo Quantitative Study Of Sized-Dependent Transport And Toxicity Of Single Silver Nanoparticles Using Zebrafish Embryos, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Tanvi Desai, Pavan K. Cherukui, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess distinctive physicochemical properties (e.g., small sizes and high surface area-to-volume ratios) and promise a wide variety of applications, ranging from the design of high quality consumer products to effective disease diagnosis and therapy. These properties can lead to toxic effects, potentially hindering advances in nanotechnology. In this study, we have synthesized and characterized purified and stable (nonaggregation) silver nanoparticles (Ag NPs, 41.6 ± 9.1 nm in average diameter) and utilized early developing (cleavage-stage) zebrafish embryos (critical aquatic and eco- species) as in vivo model organisms to probe the diffusion and toxicity of Ag NPs. We found that single …

Severe Lamotrigine Neurotoxicity Treated With Intralipid Emulsion Therapy, Philip W. Moore Do, Megan C. Urquhart Do, Dale L. Mcmillion Do, Keith K. Burkhart Md, Louis R. Cantilena Jr, Md, J Ward Donovan Md

Department of Emergency Medicine

No abstract provided.

Rice Consumption Contributes To Arsenic Exposure In Us Women, Diane Gilbert-Diamond, Kathryn L. Cottingham, Joann F. Gruber, Tracy Punshon, Vicki Sayarath, A. Jay Gandolfi, Emily R. Baker, Brian P. Jackson, Carol L. Folt, Margaret R. Karagas

Dartmouth Scholarship

Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n …

Arsenic Represses Myogenesis And Neurogenesis Through Epigenetic Mechanisms, Repressed Transcription Factors, And Altered Wnt Signaling Pathway, Gia-Ming Hong

All Dissertations

Arsenic is a toxicant commonly found in water systems around the world. Evidence from epidemiological studies indicates that chronic arsenic exposure can result in cancer, central nervous system and sensory deficits, effects on development, and neuromuscular deficits. However, the molecular mechanism of arsenic's toxicity remains largely unclear. In this study, both C2C12 mouse myoblast cells and mouse embryonic stem cells (mESCs) were used as models of arsenic mediated developmental toxicity in humans to investigate the effects of sodium arsenite on cellular differentiation.
Results from our first and second studies indicate that exposure of 20nM sodium arsenite to C2C12 mouse myocyte …

Impacts Of Psychotropic Pharmaceuticals On Hybrid Striped Bass: Altered Predation Behavior As A Function Of Changes In Brain Chemistry, Joseph Bisesi

All Dissertations

Advances in Analytical Chemistry have led to the detection of low concentrations of pharmaceuticals and personal care products (PPCPs) in wastewater treatment plant effluents as well as their receiving waters. Antidepressants are routinely found among these contaminants, but have been shown to be relatively non-toxic at environmentally measured concentrations using traditional toxicity testing techniques. The neurochemical mode of action of antidepressants warrants investigation of the effects these chemicals may have on fish behavior due to the highly conserved nature of neurotransmitter transporter targets. Using a predator prey bioassay designed in our laboratory, previous studies has shown that the antidepressant fluoxetine …

Manganese Superoxide Dismutase: Guardian Of The Powerhouse, Aaron K. Holley, Vasudevan Bakthavatchalu, Joyce M. Velez-Roman, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese …

Lentiviral-Mediated Rnai Knockdown Yields A Novel Mouse Model For Studying Cyp2b Function, Basma Damiri

All Dissertations

The Cyp2b subfamily contains five members (Cyp2b9, Cyp2b10, Cyp2b13, Cyp2b19, and Cyp2b23) of which three (Cyp2b9, Cyp2b10, Cyp2b13) are hepatic enzymes involved in xenobiotic detoxification. In this study, we made a Cyp2b-knockdown mouse using lentiviral-promoted shRNA homologous to all five Cyp2b subfamily members in FVB/NJ mouse to characterize Cyp2b's role in xenobiotic detoxification. We assessed the in vivo function of Cyp2bs in the toxicity from pesticides (i.e. parathion) and drugs (i.e. zoxazolamine). We demonstrated that Cyp2b isoforms play a key role in parathion and Zoxazolamine metabolism and toxicity. In addition, we in partially phenotyped and characterized Cyp2b-KD model and assessed …

Identifying And Reducing Lead Exposure Associated With The Use Of Cultural Practices In Southern Nevada Hispanic Communities, Maria Castillo-Couch

UNLV Theses, Dissertations, Professional Papers, and Capstones

Despite large amounts of national data on lead and childhood lead poisoning, the status of childhood lead exposure in Nevada as a result of the use of cultural practices in the Hispanic population is unknown. The influx of immigrant Hispanic populations to Nevada, their low education level, the high number of them who are living in poverty present an increased risk for children to be exposed to lead through the use of imported consumables, home remedies and alternative medicine (i.e., healers/ sobadores).

A 61-question survey collected data from Hispanics over 18 years of age who have or take care …

Phenethyl Isothiocyanate Exhibits Antileukemic Activity In Vitro And In Vivo By Inactivation Of Akt And Activation Of Jnk Pathways, N. Gao, Amit Budhraja, S. Cheng, E.-H. Liu, J. Chen, Z. Yang, D. Chen, Zhuo Zhang, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively …

P53 Regulates Oxidative Stress-Mediated Retrograde Signaling: A Novel Mechanism For Chemotherapy-Induced Cardiac Injury, Joyce M. Velez, Sumitra Miriyala, Ramaneeya Nithipongvanitch, Teresa Noel, Chotiros D. Plabplueng, Terry Oberley, Paiboon Jungsuwadee, Holly Van Remmen, Mary Vore, Daret K. St Clair

Toxicology and Cancer Biology Faculty Publications

The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin (DOX), a potent cancer chemotherapeutic drug. The production of ROS by DOX has been linked to DNA damage, nuclear translocation of p53, and mitochondrial injury; however, the causal relationship and molecular mechanisms underlying these events are unknown. The present study used wild-type (WT) and p53 homozygous knock-out (p53(-/-)) mice to investigate the role of p53 in the crosstalk between mitochondria and nucleus. Injecting mice with DOX (20 mg/kg) causes oxidative stress …

The Role Of Xpg In Processing (Cag)N/(Ctg)N Dna Hairpins, Caixia Hou, Tianyi Zhang, Lei Tian, Jian Huang, Liya Gu, Guo-Min Li

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: During DNA replication or repair, disease-associated (CAG)n/(CTG)n expansion can result from formation of hairpin structures in the repeat tract of the newly synthesized or nicked DNA strand. Recent studies identified a nick-directed (CAG)n/(CTG)n hairpin repair (HPR) system that removes (CAG)n/(CTG)n hairpins from human cells via endonucleolytic incisions. Because the process is highly similar to the mechanism by which XPG and XPF endonucleases remove bulky DNA lesions during nucleotide excision repair, we assessed the potential role of XPG in conducting (CAG)n/(CTG)n HPR.

RESULTS: To determine if the XPG endonuclease is involved in (CAG)n/(CTG)n hairpin removal, two XPG-deficient cell lines (GM16024 …

Differential Subcellular Distribution Of Rat Brain Dopamine Receptors And Subtype-Specific Redistribution Induced By Cocaine., Pamela J Voulalas, John Schetz, Ashiwel S Undieh

College of Pharmacy Faculty Papers

We investigated the subcellular distribution of dopamine D(1), D(2) and D(5) receptor subtypes in rat frontal cortex, and examined whether psychostimulant-induced elevation of synaptic dopamine could alter the receptor distribution. Differential detergent solubilization and density gradient centrifugation were used to separate various subcellular fractions, followed by semi-quantitative determination of the relative abundance of specific receptor proteins in each fraction. D(1) receptors were predominantly localized to detergent-resistant membranes, and a portion of these receptors also floated on sucrose gradients. These properties are characteristic of proteins found in lipid rafts and caveolae. D(2) receptors exhibited variable distribution between cytoplasmic, detergent-soluble and detergent-resistant …

Δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 And Peptide Transporter 2*2 Haplotype May Differentially Mediate Lead Exposure In Male Children, Christina Sobin, Natali Parisi, Tanner Schaub, Marisela Gutierrez, Alma Ortega

Selected Works Temporary Series

Child low-level lead (Pb) exposure is an unresolved public health problem and an unaddressed child health disparity. Particularly in cases of low-level exposure, source removal can be impossible to accomplish, and the only practical strategy for reducing risk may be primary prevention. Genetic biomarkers of increased neurotoxic risk could help to identify small subgroups of children for early intervention. Previous studies have suggested that, by way of a distinct mechanism, d-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and/or peptide transporter 2*2 haplotype (hPEPT2*2) increase Pb blood burden in children. Studies have not yet examined whether sex mediates the effects …

The Pulmonologist's Role In Caring For Pregnant Women With Regard To The Reproductive Risks Of Diagnostic Radiological Studies Or Radiation Therapy, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Does Treatment Of Premature Labor With Terbutaline Increase The Risk Of Autism Spectrum Disorders?, Robert L. Brent Dr.

The Selected Works of Robert Brent

none

The Pulmonologist's Role In Caring For Pregnant Women With Regard To The Reproductive Risks Of Diagnostic Radiological Studies Or Radiation Therapy, Robert L. Brent Dr.

The Selected Works of Robert Brent

No abstract

The Role Of The Pediatrican In The Effort To Prevent Congenital Malformations, Robert L. Brent Dr.

The Selected Works of Robert Brent

No