The Toxicologist - Society of Toxicology

More documents

Recommendations

Info

(TCDD) induced responses were also investigated in cells treated with the indole compound alone or in combination with TCDD. Indole (500 and 1000 μM) significantly inhibited TCDD-induced CYP1A1 mRNA and protein levels and similar results were observed for 500 μM TA however the former compound was a significantly more potent AHR antagonist. In contrast IAA did not exhibit AHR antagonist activity. These results were somewhat variable among different cell lines however, it was evident that the major gut microbiome product, indole, was an AHR antagonist and this may impact AHR-dependent gut inflammatory pathways. 163 Tolfenamic Acid Inhibits Colon Cancer Cell and Tumor Growth and Downregulates Specificity Protein (Sp) Transcription Factors. S. Pathi 1 and S. H. Safe 1, 2 . 1 Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX; 2 Institute of Bioscience and Technology, Houston, TX. Introduction: Tolfenamic acid (TA) is a nonsteroidal anti-inflammatory drug (NSAID) and is a potential chemotherapeutic agent for treatment of colon cancer; however, the mechanism of action of TA is unknown and was investigated in this study. Methods: Inhibition of colon cancer cell growth and induction of apoptosis by TA was investigated using cell counting and Annexin V staining, and modulation of specificity protein (Sp) transcription factors Sp1, Sp3, Sp4 and Sp-regulated gene products was determined by western blot analysis of whole cell lysates. Mechanisms of TA-induced Sp downregulation were investigated using specific pathway inhibitors and the in vivo anticancer activity of TA was determined in athymic nude xenograft studies using RKO cells as xenografts. Results: TA induced apoptosis and decreased colon cancer cell growth and this was accompanied by caspase-dependent proteolysis of Sp1, Sp3 and Sp4 and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1 and c-MET. TA also inhibited colon tumor growth and decreased Sp1, Sp3, Sp4 and Sp-dependent gene product expression in tumors. Conclusion: TA-induced repression of Sp transcription factors and Sp-regulated genes play a role in the cancer chemotherapeutic effects of TA. Since TA acts as anticancer agent in several tumor types, results of this study suggest for the first time that TA is a potential chemotherapeutic agent for treatment of colon cancer. Clinical applications of TA alone or in combined treatment of colon cancer are enhanced since this agent is relatively non-toxic and has previously been used as a non-steroidal anti-inflammatory drug. The prior use of TA, as an NSAID will also facilitate approval of the drug for application as a cancer therapeutic agent. 164 Ni + 2-Induced Chromosome Aberrations/Gene Amplification/Gene Silencing Alter Cytoskeleton, Ca + 2 Distribution, and Global Gene Expression, Causing Morphol./Neoplast. Transformation of 10T1/2 Mouse Embryo Cells. J. R. Landolph 1, 3, 2 , A. DaSilva Pehl 2, 3 , P. Samala 1, 3 , S. Keliipaakaua 2, 3 and K. Akinwumi 1, 3 . 1 Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA; 2 Department of Pathology, University of Southern California, Los Angeles, CA; 3 USC Cancer Center, University of Southern California, Los Angeles, CA. Ni refinery workers inhaling Ni sulfidic ore dusts/smoking cigarettes contracted lung/nasal cancers. Inhaled Ni3S2/green NiO induced lung cancer in rats. Ni3S2/green-black NiOs induced chromosome aberrations/morph-neoplas transformation (Tx) in 10T1/2 mouse cells. Ni/MCA-Tx cell lines showed a) ect-2 gene amplification/higher ect-2 mRNA/protein, b) no DRIP80 c) no β-centaurin-2 mRNA. We hypothesized Ni+2 1) amplified ect-2 gene, causing higher levels of microtubules (MTs); 2) silenced β-centaurin-2 gene, causing higher levels of microfilaments (MFs); and 3) silenced DRIP gene, altering Ca+2 distribution/Tx 10T1/2 cells. We tested these hypotheses by staining cells with fluor. phalloidin to decorate MFs; fluor. Ab to α-tubulin to decorate MTs; Fluo 3AM to stain Ca+2; DAPI to decorate nuclei; then examined cells by confocal microscopy. In non-Tx 10T1/2 cells, MFs/MTs were arranged in long fibers. In NiS/green NiO-Tx cell lines, MFs/MTs were over-expressed, aggregated in areas, absent/other areas, changing cell shapes. Low density non-Tx cells had high nuclear/low cytoplasmic Ca+2 concentrations (State I); high density near-confluent cells had low nucl./high cyto. Ca+2 (State II). Ni/MCA-Tx cell lines were largely in State II. We conclude Ni+2 ions 1) amplified ect-2/silenced β-centaurin-2 genes, causing over-expression of MTs/MFs, altering cell shapes, changing global gene expression; 2) silenced DRIP80 gene, altering Ca+2 distributions in Tx cells; and 3) induced mutations/methylations in 15 genes, causing differential expression of 130 genes, contributing to induction/maintenance of Tx phenotypes in Ni+2/MCA-Tx cell lines. Support: R01 ES03341/NIEHS (PI JRL); Cancer Center Core Grant 5 P30 CA09320/NCI; MS Program/Discret. Funding (JRL). 34 SOT 2013 ANNUAL MEETING 165 Benzoquinone-Induced Topoisomerase Modifications: Linking Benzene Myelotoxicity and Leukemia. C. L. Kuhlman, G. Tsaprailis, T. J. Monks and S. S. Lau. Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ. Protein adduction by reactive electrophiles can induce structural and functional changes that contribute to toxicity and disease progression. Such electrophiles are often products of xenobiotic metabolism or generated endogenously via oxidative stress and lipid peroxidation. Relevant to this phenomenon are the redox-active and electrophilic metabolites of benzene, which are believed to contribute to its myelotoxic effects. When the benzene metabolites hydroquinone (HQ) and phenol (PHE) are administered to rats, HQ oxidizes to 1,4-benzoquinone (BQ) and in the presence of GSH gives rise to multi-GSH conjugates detectible in bone marrow. These HQ-GSH conjugates retain the ability to adduct proteins and to redox cycle. Here we report that bone marrow malondialdehyde levels in PHE/HQ treated rats are significantly elevated, indicative of lipid peroxidation and the consequent generation of other reactive electrophilic aldehydes, such as 4-hydroxy-2-nonenal (4HNE). Indeed, proteomics profiling revealed bone marrow proteins targeted by benzene metabolites and 4HNE, including 14-3-3 protein zeta/delta, protein disulfide isomerase A3, peroxiredoxin 2, and calreticulin. Adduction of topoisomerase II α (topo IIα) has been implicated in benzene-induced leukemia, and cancer chemotherapeutic topo IIα inhibitors are a leading cause of therapy-induced leukemia. We next reacted purified topo IIα (6 units) with BQ (0.5 μM) or 4HNE (1.3 μM). A marked reduction in the ability of topo IIα to decatenate the kDNA substrate was observed. Proteomic analysis of 4HNE-reacted topo IIα revealed multiple amino acid sites of adduction, including K893 and K1480 adducts. Adduction of these lysine residues could impair topo IIα-DNA binding, or inhibit topo IIα’s ATP-dependent formation and annealing of DNA strand breaks. The consequences of BQ- and 4HNE-induced functional alterations in topo IIα are currently under investigation. 166 Overexpression of CRM1 in Normal Human Lung Epithelial Cells Changes Cellular Morphology and Cytotoxic Responses to Tobacco-Specific Carcinogen NNK. C. Lu, W. Zhu and W. Gao. The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX. Chromosome region maintenance 1 (CRM1), the major nuclear export receptor with a broad substrate range, is not only required for transport of many RNAs and proteins but also involved in various modulations within the cell such as mitosis, cell arrest, and apoptosis. Our recently published study showed that CRM1 played critical roles in response to tobacco-specific carcinogen, 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK), in BEAS-2B cells (a normal human lung epithelial cell line). The objective of the present study was to further examine the significance of CRM1 in lung cancer development using BEAS-2B cells stably overexpressing CRM1 (BEAS-2BCRM1+ cells). The overexpression of CRM1 in BEAS- 2BCRM1+ cells was confirmed by real-time PCR and western blot. As compared to BEAS-2B cells, BEAS-2BCRM1+ cells were prone to form colonies. Soft-agar assay further demonstrated increased colony formation and larger colony size in BEAS- 2BCRM1+ cells in comparison with BEAS-2B cells. In addition, the cytotoxic effects in response to NNK was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay in both cells. Cells were treated with 0-500 μM NNK for 24, 48, and 72 h. The inhibitory effects were dose and time dependent in both cells (p
signaling. ARNT is expressed as two isoforms, isoform 1 and 3, but whether these isoforms differentially regulate NF-κB activity is unclear. Isoform 1 is identical to isoform 3 except for an additional 15 amino acids near the N-terminus. The extra amino acids in isoform 1 provide a phosphorylation site, which has been shown to inhibit its DNA binding. Interestingly, we have observed in lymphoid malignancies that ARNT isoform 1 is expressed at much higher levels than isoform 3 as compared to normal lymphocytes where the ARNT isoforms are expressed at equal levels. We find that ARNT isoform 1 potentiates while ARNT isoform 3 abrogates NF-κB activity. In light of our previous ARNT-RelB model, these opposing effects of the ARNT isoforms in NF-κB signaling appear to hinge on their ability to associate with RelB as ARNT isoform 3 binds much more strongly than isoform 1. Lastly, we found that the co-expression of a GFP-tagged p100 in combination with the ARNT isoforms promoted p100 nuclear translocation, possibly through a RelB bridge, resulting in diminished transactivation of NF-κB responsive genes. Thus, our current working model is one in which lymphoid malignancies shift toward the production of ARNT isoform 1, which in turn enhances NF-κB activity, as a contributing factor to their growth and survival. 168 Co-Exposure to Arsenic and Estrogen Leads to Enhanced Transformation of Normal Human Prostate Epithelial Cells. J. Treas, T. Tyagi and K. P. Singh. The Institute of Environmental and Human Health, Texas Tech, Lubbock, TX. Exposure to both arsenic and estrogen are known risk factors for prostate cancer, however the carcinogenic effect of their co-exposure is not known. Therefore, the objective of this study was to evaluate the transformation potential and its mechanism in human prostate epithelial cells by co-exposure to these two chemicals. To achieve this objective, the human prostate epithelial cells, RWPE-1 were treated for 6 months with sodium-meta arsenite and 17β-estradiol, both alone and in combination, at concentrations of 100 pg/mL and 100 ng/mL. Cell counts and MTT assay was performed to determine the effects on growth, and soft agar assay was performed to evaluate the cell transformation by exposure to arsenic and estrogen. Potential role of estrogen receptors and aromatase in mediating the cellular response to these chemicals was evaluated by measuring their expression at transcript level. The result of this study revealed that the growth and transformation of RWPE-1 cells were significantly greater in arsenic and estrogen co-exposed cells as compared to cells individually exposed to these two chemicals. The data of quantitative real time PCR revealed that expression of estrogen receptor beta was significantly increased whereas aromatase was significantly decreased in arsenic and estrogen co-exposed cells. These findings together with our recently published data on aberrant expression of epigenetic regulatory genes, such as, DNMTs, HDACs and MBDs in arsenic and estrogen co-exposed cells suggest that co-exposure to these two chemicals enhances carcinogenicity through epigenetic mechanisms. 169 Effects of Polycyclic Aromatic Hydrocarbons with Estrogen Receptors α and β in Breast Cancer Cells. T. T. James 1, 2 , C. K. Sievers 2 , E. Shanle 1, 2 , S. S. Hecht 3 , C. A. Bradfield 1, 2 and W. Xu 1, 2 . 1 Molecular and Environmental Toxicology Center, University of Wisconsin- Madison, Madison, WI; 2 Oncology, University of Wisconsin-Madison, Madison, WI; 3 Masonic Cancer Center, University of Minnesota, Minneapolis, MN. Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants found in cigarette smoke, contaminated soil, vehicle exhaust, among others, known to cause adverse health effects including carcinogenesis and endocrine disruption. The metabolites of PAHs have been implicated in endocrine disruption. Some PAHs are known to have estrogenic effects by interacting with estrogen receptors (ERs). Estrogens have diverse roles including regulation of mammary gland development and morphogenesis, and maturation of uterus and ovaries. These functions are mediated by two subtypes of estrogen receptors, ERα and ERβ, which function in dimer forms (i.e. ER α,β homodimers and ERα/β heterodimers).ERα is known to be proliferative while ERβ is known to be antiproliferative in the mammary gland. The estrogenic effects of PAHs have been mostly focused on their effects on ERα. Recently our lab reported that the monohydroxylated metabolites of naphthalene, phenanthrene and pyrene showed differential effects with ERα and ERβ. These PAHs were selected because they are found at high levels in contaminated environments. The ability of the PAH compounds to promote estrogenic effects were revealed by luciferase assays in isogenic reporter cell lines, competitive binding assays and bioluminescent resonance transfer (BRET) assays. The PAHs metabolites were more selective for ERβ and were able to activate ERβ target genes suggesting that these compounds can interfere with ERβ signaling in human breast cancer cells. In this study we screened additional PAHs and their monohydroxylated metabolites to determine their estrogenic effects. These studies demonstrate the impact of monohydroxylated PAHs on ER signaling and provide basis for the determination of the effects of other environmental compounds on ER. Supported by NIEHS Predoctoral Training Grant T32 ES007015 170 Alternative Splicing of ATG5 in DU145 Human Prostate Cancer Cells Inactivates Autophagy and Promotes Xenograft Tumor Growth. D. J. Wible 1, 2 , T. M. Calhoun-Davis 2 , D. G. Tang 2 and S. B. Bratton 2 . 1 Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX; 2 Molecular Carcinogenesis, Virginia Harris Cockrell Cancer Research Center at The University of Texas MD Anderson Cancer Center Science Park, Smithville, TX. Autophagy is a highly conserved pathway that targets cytoplasmic cargo to the lysosome for degradation. Excess or aberrant organelles, large protein aggregates and non-selective portions of the cytosol can be targeted by the autophagosome and delivered to the lysosome in order to maintain cellular homeostasis or survival in response to stress. In this study, we show that DU145 human prostate cancer cells alternatively splice Autophagy-related protein 5 (ATG5), an essential protein for autophagosome formation. These novel ATG5 splice forms are unable to conjugate normally to ATG12 and instead are rapidly ubiquitinated and turned over by the proteasome. The absence of ATG5-ATG12 conjugate in DU145 cells prevents autophagosome formation and autophagic degradation. Stable expression of fulllength ATG5 using lentiviral infection rescued both ATG5-ATG12 conjugation and autophagy. Autophagy is currently thought to be tumor suppressive by eliminating potentially genotoxic protein aggregates and damaged organelles. However, the role it plays in tumor progression and metastasis remains unclear. To address this question, we performed subcutaneous injections of autophagy-deficient and autophagy-proficient DU145 cells into immunodeficient mice and monitored tumor formation and growth. In initial experiments, autophagy deficient tumors had a significantly longer latency period, yet grew at a faster rate than autophagy competent tumors. This suggests that autophagy can promote initial tumor establishment, while suppressing later tumor growth. Currently there are numerous clinical trials investigating the therapeutic potential of drugs that inhibit autophagy. Since it’s not yet clear how these opposing aspects affect cancer metastasis, further study is essential to ensure effective therapy. 171 The Aryl Hydrocarbon Receptor Regulation during Epithelial-to-Mesenchymal Transition. S. S. Kishinhi and S. E. Eltom. Biochemistry & Cancer Biology, Meharry Medical College, Nashville, TN. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a role as a mediator of the xenobiotic signaling pathways. Recently, the AhR emerged as a major player in breast carcinogenesis. We have shown previously that ectopic overexpression of AhR in immortalized normal human mammary epithelial cells (HMEC) resulted in the development of malignant phenotypes, most notably the epithelial-to-mesenchymal transition (EMT). This EMT phenotype however, is not rigid but is in a dynamic state; with cells moving back and forth between epithelial and mesenchymal states. We asked the question whether this flux of phenotypes is due to changes in AhR levels or activity. A clone of HMEC overexpressing AhR, with either epithelial (E) or fibroblastic (F) phenotypes was compared to an empty vector (EV) control cells. We employed Western blotting, immunocytofluorescence (ICF) staining and RT-PCR techniques to assess the AhR expression as well as the epithelial and mesenchymal markers, E-Cadherin and vimentin, respectively. Our results showed that although at the mRNA levels AhR expression was similar, the AhR protein was higher in E- than in F-type cells. The AhR protein levels were always higher when cells were grown at higher density. Nuclear localization as assessed by ICF and CYP1A1 expression as assessed by RT-real time PCR, were used as surrogates for AhR activation. Our analysis showed that AhR activation was much higher in F-type cells and is more pronounced at higher cell density. In contrast, a 3h treatment with TCDD, a potent AhR agonist resulted in a steeper induction of CYP1A1 in E-type than the F-type cells, which is further enhanced at higher density. The observed difference in AhR protein levels and activity may be due to a differential stability of the protein associated with the two morphological forms, which is under investigation. 172 Expression and Role of ALDH1B1 in Pancreatic Cancer. S. Singh 1 , K. Quackenbush 2 , A. Purkey 2 , J. Arcaroli 2 , Y. Chen 1 , D. J. Orlicky 3 , W. Messersmith 2 and V. Vasiliou 1 . 1 Department of Pharmaceutical Sciences, University of Colorado, Aurora, CO; 2 Division of Medical Oncology, University of Colorado, Aurora, CO; 3 Department of Pathology, University of Colorado, Aurora, CO. Recent studies show that ALDH activity selectively defines an enhanced tumor-initiating cell population in human pancreatic adenocarcinoma. The specific ALDH isozyme(s) contributing to the high ALDH activity in these cells are unknown. We have recently shown that the mitochondrial aldehyde dehydrogenase 1B1 SOT 2013 ANNUAL MEETING 35
Page 1 and 2: The Toxicologist Supplement to Toxi
Page 3 and 4: The Toxicologist Supplement to Toxi
Page 5 and 6: 1 A Refresher of Immunoglobulin and
Page 7 and 8: 12 Understanding Toxic Neuropathy i
Page 9 and 10: SWCNTs (raw FeSWCNT or purified cSW
Page 11 and 12: 34 Computational Systems Biology Mo
Page 13 and 14: driving allergic airway response, c
Page 15 and 16: E100, E0 vapors caused no overt mat
Page 17 and 18: in heart rate, blood pressure, brea
Page 19 and 20: hearts showed a coronary artery dis
Page 21 and 22: inducible NADPH oxidase dependent m
Page 23 and 24: 93 Simulated Metabolism in the Lang
Page 25 and 26: (female pubertal assay, OPPTS 890.1
Page 27 and 28: 112 Endocrine Disruption Potential
Page 29 and 30: The incorporation of in vitro data
Page 31 and 32: was validated by the following resu
Page 33 and 34: 139 A Systematic Analysis of ToxCas
Page 35 and 36: 148 Mucosa-Associated Enteropathoge
Page 37: 158 The Cannabinoid WIN 55, 212-2 D
Page 41 and 42: 177 Modifying Effect of Glycidol Fa
Page 43 and 44: 24 and 72 hours post treatment. We
Page 45 and 46: line and the effects of the haploty
Page 47 and 48: organ weight, gross findings, or hi
Page 49 and 50: 215 Acute and Delayed Effects of In
Page 51 and 52: 224 Interaction of Human Bronchial
Page 53 and 54: espiratory and olfactory mucosal le
Page 55 and 56: hyperresponsiveness to MCh aerosol
Page 57 and 58: shown that the collagen content is
Page 59 and 60: fect is consistently higher in male
Page 61 and 62: surrogate) in the presence or absen
Page 63 and 64: of field controls were 46.3 ± 5 μ
Page 65 and 66: 290 Interpretation of Multiroute Da
Page 67 and 68: 18.8 ml/min/kg) were more similar t
Page 69 and 70: Urinary excretion at 72 h post admi
Page 71 and 72: into a physiologically based pharma
Page 73 and 74: 327 Cytochrome P450 Gene Transcript
Page 75 and 76: (LD50 = 25 μM). Both pre- and post
Page 77 and 78: 345 Prediction of Human Equivalent
Page 79 and 80: only remnants, including utriculi a
Page 81 and 82: 363 MicroRNA Microarray Analysis of
Page 83 and 84: 371 Mechanisms of Vesicating Agent
Page 85 and 86: 381 Effect of Asbestos Exposure on
Page 87 and 88: PCB126 at doses of 0.1; 1 or 10μg/
Page 89 and 90:
399 Immunotoxicity of the Nasal Ass
Page 91 and 92:
407 The Dermal Exposure to Silica N
Page 93 and 94:
416 Exposure to Triclosan Augments
Page 95 and 96:
ventilation. Two independent method
Page 97 and 98:
the German Federal Ministry of Educ
Page 99 and 100:
443 Sonolytic Degradation of Pluron
Page 101 and 102:
mice were anesthetized and lungs an
Page 103 and 104:
mulations propelled the development
Page 105 and 106:
fluorophore was removed by ultrafil
Page 107 and 108:
The objective of this study was: (1
Page 109 and 110:
489 Preliminary Toxicokinetics of N
Page 111 and 112:
were twice as much susceptible to d
Page 113 and 114:
improve the fit to the available in
Page 115 and 116:
lead to i) a significant reduction
Page 117 and 118:
(CYP1A1). Induction of this enzyme
Page 119 and 120:
We have described a role for miRNAs
Page 121 and 122:
individual treatment. Both compound
Page 123 and 124:
554 Toxicogenomic Analysis of Envir
Page 125 and 126:
563 Global Gene Expression Changes
Page 127 and 128:
572 Preliminary Steps in a Whole Mi
Page 129 and 130:
581 Chemical Characterization of Co
Page 131 and 132:
fungicides. Studies indicated that
Page 133 and 134:
of the used soil. Mortality and som
Page 135 and 136:
from repeated doses, and the utilit
Page 137 and 138:
618 Use of a Physiologically-Based
Page 139 and 140:
emained as such through 24 hours po
Page 141 and 142:
number of hepatic neutrophils remai
Page 143 and 144:
human PRL (150 ng/ml) or human PL (
Page 145 and 146:
time and Nrf2 -dependent increase i
Page 147 and 148:
664 Hepatic Flavin-Containing Monoo
Page 149 and 150:
673 Hypoxia Perturbs PCB-Induced Ar
Page 151 and 152:
factor tool predicted the activatio
Page 153 and 154:
to 50 μM Cd for 4 or 8 hours. Glob
Page 155 and 156:
701 Reprogramming of the HepG2 Geno
Page 157 and 158:
a process that was tested using di(
Page 159 and 160:
a. Integrated Mode-of-Action (MoA)
Page 161 and 162:
MitoPark mice also showed a dramati
Page 163 and 164:
738 Human Antibodies Can Cross Guin
Page 165 and 166:
Based on an initial 2 day dose-resp
Page 167 and 168:
non-invasive methodology to measure
Page 169 and 170:
768 Air Quality Impacts of Natural
Page 171 and 172:
pathology by disrupting the normal
Page 173 and 174:
pathways. Through these activities
Page 175 and 176:
Approval of the Medical Research Et
Page 177 and 178:
ile duct hyperplasia and hepatocell
Page 179 and 180:
degradation enzymes, matrix metallo
Page 181 and 182:
825 Image-Derived Models of Subcell
Page 183 and 184:
used a number of strategies to mani
Page 185 and 186:
ange of the population. It is gener
Page 187 and 188:
858 Flexible and Transparent Comput
Page 189 and 190:
available tool that provides a foun
Page 191 and 192:
876 Web-Based Benchmark Dose Modeli
Page 193 and 194:
885 A Mechanistic Approach to Under
Page 195 and 196:
observed pharmacokinetic difference
Page 197 and 198:
Funding: EU-FP7 (ENFIRO; grant agre
Page 199 and 200:
913 Protective Role of Carnosine Ag
Page 201 and 202:
measurable neurobehavioral endpoint
Page 203 and 204:
For the TLDA- derived PCR data, a m
Page 205 and 206:
samples within each group, strongly
Page 207 and 208:
950 Smoking-Induced microRNA Change
Page 209 and 210:
IL-1α. This approach has been adva
Page 211 and 212:
969 Collaborative Project in JCIA f
Page 213 and 214:
977 Predicting Eye Irritation of Ag
Page 215 and 216:
organophosphates, organochlorines,
Page 217 and 218:
996 Does the Barker Hypothesis Appl
Page 219 and 220:
1005 Effects of Di(2-Ethylhexyl)-Ph
Page 221 and 222:
compared to single housing. In conc
Page 223 and 224:
1023 Hyperactivity of Rat and Mouse
Page 225 and 226:
1 and Rho kinase inhibitor (HA1077)
Page 227 and 228:
and subcutaneous and/or dermal infl
Page 229 and 230:
inding in the liver, which involves
Page 231 and 232:
tion, glycolysis, and amino acid me
Page 233 and 234:
was isolated from frozen samples, a
Page 235 and 236:
1079 MicroRNA Regulation of Alcohol
Page 237 and 238:
an inducer of hyperglycemia) to cha
Page 239 and 240:
1097 Deletion of Hepatocyte Nuclear
Page 241 and 242:
study, we validated this short-term
Page 243 and 244:
ferentiation and glucose metabolism
Page 245 and 246:
tients treated with desipramine, th
Page 247 and 248:
from mesenteric and uterine vascula
Page 249 and 250:
Akt2 function preservation. For mec
Page 251 and 252:
1152 Serum and Hepatic Alkaline Pho
Page 253 and 254:
fold) with a dissociation constant
Page 255 and 256:
1171 Fin Whale Cells Are More Resis
Page 257 and 258:
develop analytical means to measure
Page 259 and 260:
and location of ROS, and 2) cell an
Page 261 and 262:
25% of patients receiving Imatinib
Page 263 and 264:
lesions originate from is not clear
Page 265 and 266:
Our analysis detected and corrected
Page 267 and 268:
and APC. Results: Etirinotecan pego
Page 269 and 270:
to the amount of fecal contaminatio
Page 271 and 272:
1243 A High-Throughput Analytical M
Page 273 and 274:
1252 Using Doubly-Labeled Water Ene
Page 275 and 276:
implying that BPA is toxic to human
Page 277 and 278:
1271 The Aryl Hydrocarbon Receptor
Page 279 and 280:
1280 Aryl Hydrocarbon Receptor (AhR
Page 281 and 282:
genes, suggesting a role for AHRRa
Page 283 and 284:
and cellular proliferation. Underst
Page 285 and 286:
1307 Toxicological Evaluation of th
Page 287 and 288:
in blood as confirmed by a componen
Page 289 and 290:
activation of scavenger receptor B
Page 291 and 292:
AgNPs in dilutions of an environmen
Page 293 and 294:
after dosing for TEM analysis. Imag
Page 295 and 296:
various cell-lines. However, the da
Page 297 and 298:
and the presence of leukocytes and
Page 299 and 300:
1374 PCB 95 and IFN-gamma Exert Opp
Page 301 and 302:
on estrogens. It is not known how t
Page 303 and 304:
cell number, was reduced at PND10,
Page 305 and 306:
1402 Repeated Exposure to Paraquat
Page 307 and 308:
weeks (3 injections/week). We recor
Page 309 and 310:
1421 Differential Antagonism of Tet
Page 311 and 312:
of the syringe suggesting loss due
Page 313 and 314:
1439 Interleukin 17 Responses Induc
Page 315 and 316:
strains were exposed in triplicate
Page 317 and 318:
1458 An In Vitro Placental Model Us
Page 319 and 320:
Phagotest® (Glycotope Biotechnolog
Page 321 and 322:
1477 Use of An In Vitro Flow Cytome
Page 323 and 324:
1487 Evaluation of Genotoxicity of
Page 325 and 326:
commonly used in textile industry.
Page 327 and 328:
under hamster S9-activated and non-
Page 329 and 330:
neutrophilic to eosinophilic respon
Page 331 and 332:
1524 The Palmitoylation of Meh1, a
Page 333 and 334:
for Dark, Pb afforded 0.607 mg/kg f
Page 335 and 336:
to 5.4 or 54.1 mg/m3, respectively)
Page 337 and 338:
1552 Body-Residue Based Environment
Page 339 and 340:
1561 Identifying No Observed Effect
Page 341 and 342:
studies/endpoints led by academic i
Page 343 and 344:
1580 In Vitro Episkin Skin Corrosio
Page 345 and 346:
RXR, opening the possibility that t
Page 347 and 348:
1601 Enhanced Susceptibility of Fat
Page 349 and 350:
potential to impact the safety asse
Page 351 and 352:
A dataset of over 200 compounds cov
Page 353 and 354:
that link in vivo outcomes (includi
Page 355 and 356:
in humans, occurring in eight newbo
Page 357 and 358:
novel mechanisms of action where th
Page 359 and 360:
their homes, learn about historic a
Page 361 and 362:
toxicology where Tox-21c could have
Page 363 and 364:
compounds and Colcemide as an aneug
Page 365 and 366:
dose dependent increases (p< 0.05)
Page 367 and 368:
1707 Dose Response and Temporality
Page 369 and 370:
several cells, including cancer cel
Page 371 and 372:
1727 Characterization of Cigarette
Page 373 and 374:
1736 Coating Nanoporous Alumina: Ce
Page 375 and 376:
1745 Comparison of Toxicity of Bare
Page 377 and 378:
using microscopy, cytotoxicity test
Page 379 and 380:
ona, and 1.8 folds lower than the d
Page 381 and 382:
RESULTS: Electronic microscopy stud
Page 383 and 384:
effect of its flavonolignans. Becau
Page 385 and 386:
These results suggest that mollugin
Page 387 and 388:
m266.2 were not different from thos
Page 389 and 390:
and associated drug accumulation, w
Page 391 and 392:
1820 Application of Canine Kidney T
Page 393 and 394:
1829 Effect of Body-Weight Loading
Page 395 and 396:
mechanisms of cell death, we invest
Page 397 and 398:
post-translational modifications of
Page 399 and 400:
as oxidative stress, Ca2+ dysregula
Page 401 and 402:
studies assessing cognitive and mot
Page 403 and 404:
spine density of hippocampal pyrami
Page 405 and 406:
individually or in combinations, in
Page 407 and 408:
1893 A Comparative Study on Renal T
Page 409 and 410:
same hand and between washed and no
Page 411 and 412:
1911 Molecular, Cellular, and Histo
Page 413 and 414:
1920 Endocrine Modulatory Effects o
Page 415 and 416:
CYP19 mRNA levels were observed wit
Page 417 and 418:
males and females. In efforts to bl
Page 419 and 420:
worker’s capacity to adapt to hea
Page 421 and 422:
from different studies indicates th
Page 423 and 424:
1966 Associations between Carcinoge
Page 425 and 426:
1975 Assessment of the Impacts of C
Page 427 and 428:
For this analysis, nine PCBs with d
Page 429 and 430:
1993 PBDE-100 Induces Mitochondrial
Page 431 and 432:
2002 Cyp1b1-Deficiency Alters Struc
Page 433 and 434:
enzymes and xenobiotic transporters
Page 435 and 436:
protected against p-aminophenol (PA
Page 437 and 438:
status has shown much promise. Howe
Page 439 and 440:
esidues in proteins. The significan
Page 441 and 442:
where no peak (same action througho
Page 443 and 444:
were exposed to ethyl-alcohol via t
Page 445 and 446:
2066 Validation of a 7-Color Flow C
Page 447 and 448:
tive and detoxification genes. In a
Page 449 and 450:
activated B cells and BCL-6, a tran
Page 451 and 452:
later time points. Therefore, BPA e
Page 453 and 454:
2102 Brominated Diphenyl Ether-47 I
Page 455 and 456:
distribution and excretion or other
Page 457 and 458:
serum Inhibin B was never changed.
Page 459 and 460:
2130 Structural Changes in Various
Page 461 and 462:
Methods: Adult male Fisher 344 rats
Page 463 and 464:
asked what genes are involved in Me
Page 465 and 466:
study examined whether combined Pb+
Page 467 and 468:
elated to dried blood spots and mas
Page 469 and 470:
15(R) D2 increased by 3.3 / 2.3-fol
Page 471 and 472:
otic transcription factors nuclear
Page 473 and 474:
genes. On the other hand, the creat
Page 475 and 476:
2203 Resistance to Dioxin-Induced H
Page 477 and 478:
data because the human data were no
Page 479 and 480:
odent cancer bioassay of MTBE in dr
Page 481 and 482:
(BMCL) estimates were extrapolated
Page 483 and 484:
outcomes which differ from those ou
Page 485 and 486:
2250 Validation of the Yeast Estrog
Page 487 and 488:
in cell index, indicative of cytoto
Page 489 and 490:
platform maybe most appropriate for
Page 491 and 492:
200, 1000, or 2000 parts per billio
Page 493 and 494:
2288 Paradoxical Effects of Ongoing
Page 495 and 496:
for intracellular tracking of GR us
Page 497 and 498:
2306 Evaluating Arsenic Speciation
Page 499 and 500:
2316 Integrative Toxicopathological
Page 501 and 502:
improve food safety is to reduce ex
Page 503 and 504:
ased on human oral challenge studie
Page 505 and 506:
2344 The Global Burden of Disease C
Page 507 and 508:
HDACs had opposite effects, suggest
Page 509 and 510:
useful in human health risk assessm
Page 511 and 512:
1.7% in mucosal side. These results
Page 513 and 514:
2381 Silica Nanoparticles Induce Ac
Page 515 and 516:
have been well-demonstrated to be o
Page 517 and 518:
2400 Fibrinogen: A New Kid on the B
Page 519 and 520:
all critical factors. Vital organ s
Page 521 and 522:
identifying QSARs that are applicab
Page 523 and 524:
after the training, and the percent
Page 525 and 526:
sham control group was included to
Page 527 and 528:
after 15 min incubation with the C8
Page 529 and 530:
2462 Nonhuman Primate Sexual Maturi
Page 531 and 532:
2472 Modeling Human Genetic Variabi
Page 533 and 534:
two subgroups, hippocampus were dis
Page 535 and 536:
2495 Physiologically-Based Pharmaco
Page 537 and 538:
plexes with important functional gr
Page 539 and 540:
Notes SOT 2013 AnnuAl MeeTing 535
Page 541 and 542:
Author Index (Continued) B Baan, R
Page 543 and 544:
Author Index (Continued) Cassis, L
Page 545 and 546:
Author Index (Continued) Dodmane, P
Page 547 and 548:
Author Index (Continued) Gilpin, S
Page 549 and 550:
Author Index (Continued) Huh, G 18
Page 551 and 552:
Author Index (Continued) Krantz, Q
Page 553 and 554:
Author Index (Continued) Martin, S
Page 555 and 556:
Author Index (Continued) Niklas, J
Page 557 and 558:
Author Index (Continued) Rana, P 2
Page 559 and 560:
Author Index (Continued) Shin, K 6
Page 561 and 562:
Author Index (Continued) Touissant,
Page 563 and 564:
Author Index (Continued) Wormser, U
Page 565 and 566:
Abstract Keyword Index (Continued)
Page 567 and 568:
Page 569 and 570:
Page 571 and 572:
Page 573 and 574:
Page 575 and 576:
Page 577 and 578:
Page 579 and 580:
e O cial Journal of the Society of
show all

The Toxicologist - Society of Toxicology

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?