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DNA assay corroborated the DASL data. This work showed that the use of degraded RNA from FFPE blocks for microarray studies is possible. Therefore, retrospective analysis without the need for new animal studies could be enabled by using FFPE samples. Furthermore, in studies with unexpected organ toxicities were no fresh frozen tissue is available, toxicogenomic evaluations are still possible and can support mechanistic interpretations. 1591 TRANSCRIPTIONAL DOSE RESPONSE ANALYSIS IN FEMALE MOUSE AND RAT LUNGS FOLLOWING REPEATED INHALATION EXPOSURE TO 2-CHLORO-1, 3-BUTADIENE. M. W. Himmelstein 1 and R. S. Thomas 2 . 1 DuPont Haskell Global Centers, Newark, DE and 2 The Hamner Institutes for Health Sciences, Research Triangle Park, NC. Beta-chloroprene (2-chloro-1,3-butadiene), a monomer used in the production of neoprene elastomers, is of regulatory interest due to the production of mouse lung tumors in a two-year rodent bioassay. A significant increase in female mouse lung tumors was observed at 12.8 ppm while a small, but statistically insignificant increase was observed in female rats at 80 ppm. Gene expression microarray and histopathological analysis were performed in the lungs of female mice following exposure at 0.3, 3, 13, and 90 ppm and in female rats following exposure at 5, 30, 90, and 200 ppm. The exposures were selected to span the rodent bioassay concentrations and provide approximately equal target tissue doses in the lung based on total amount metabolized per gram tissue. Exposures were performed for a period of 5 and 15 days. For the mouse, minimal hyperplasia was observed in the terminal bronchioles after 5- and 15 days of exposure at 90 ppm. No significant histopathological changes were observed at any exposure concentration in the female rat lung. Based on traditional analysis of variance, the number of genes with significantly altered expression in the mouse lung at the 5- and 15-day time points was similar and increased with dose. In the rat lung, the number of significantly altered genes was higher at the 5-day time point. Benchmark dose (BMD) methods were used to model the transcriptional dose-response data and calculate dose estimates at which different signaling pathways were altered. The BMD values for the selected signaling pathways were filtered to identify those with a transcriptional dose-response consistent with the tumor response in the rodent bioassay. A small subset of signaling pathways were identified and included changes in glutathione metabolism, oxidative stress, mismatch DNA repair, and amino acid metabolism. The results serve to identify potential modes-of-action for chloroprene for follow-up study. 1592 GENE EXPRESSION PROFILING OF LXR-MEDIATED HEPATIC STEATOSIS IN RATS. J. M. Maher, W. R. Buck, M. J. Liguori, J. Lai-Zhang, T. Sharapova, S. J. Morgan, E. A. Blomme and Y. Yang. Investigative Toxicology and Pathology, Abbott Laboratories, Abbott Park, IL. The Liver-X Receptor (LXR) is a nuclear receptor that is activated by oxysterols, and LXR mediates key steps in bile acid synthesis. T0901317 is a potent LXR agonist known to markedly increase liver weights, induce fatty acid synthesis, and cause significant hepatic steatosis. The purpose of the current study was to evaluate gene expression changes caused by T0901317 to identify unique genes regulated by LXR agonists that differentiate this profile from other steatotic compounds or from changes observed in starvation-induced steatosis. In the current study, Sprague- Dawley rats were dosed with T0901317 for five days at dosages of 5, 25, and 50 mg/kg/day in PEG400:Tween 80 (80:20 w/w). Livers were collected for both pathology and toxicogenomics, and serum was collected for clinical chemistry. Liver triglycerides (TGs) were markedly increased in a dose-dependent manner, yet serum TGs were significantly decreased after 5 days in an inverse manner, a finding which is seemingly species or timepoint specific when compared to mice. T0901317 caused marked induction of pathways related to sterol regulatory element-binding protein 1-C (SREBP-C) signaling, and these gene changes are generally related to increases in fatty acid and cholesterol biosynthesis. LXR-induced steatosis clustered away from other steatotic models due to marked induction of a few key genes involved in beta-oxidation, including CD36, malic enzyme, SREBP- C, and long chain fatty acyl-CoA synthetase. Furthermore, Angiopoietin-like 3, a key gene in determining serum TG levels in rodents, was not upregulated in response to T0901317 treatment, coinciding with the observed findings. Through gene profiling, recognition of LXR agonism by microarray allows for an early signal that may aid in the prediction of steatosis, which can then trigger the further characterization of experimental compounds that may have LXR-mediated effects on the liver. 342 SOT 2011 ANNUAL MEETING 1593 CHARACTERIZATION OF THE HEPATIC TRANSCRIPTOME RESPONSE TO A MIXTURE OF LOW MOLECULAR WEIGHT POLYBROMINATED DIPHENYL ETHERS: DISEASE, SIGNATURE, NETWORK, AND PATHWAY ANALYSIS. S. S. Auerbach 1 , K. R. Shockley 1 , R. Thomas 2 , N.J.Machesky 4 , M. K. Vallant 1 , C. D. Hebert 3 , H. C. Cunny 1 and J. K. Dunnick 1 . 1 National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 2 Environmental Health Sciences, University of California, Berkeley, CA, 3 Southern Research Institute, Birmingham, AL and 4 Battelle Columbus Operations, Columbus, OH. Polybrominated diphenyl ethers (PBDEs) are widespread persistent organic pollutants that produce toxicity in the liver, thyroid and brain. As a part of the ongoing NTP studies of the PBDEs, liver transcriptome analysis was performed on liver samples from 22-day old male rats exposed by gavage to a mixture of low molecular weight PBDEs from gestation day 6 to postnatal day 21. Disease-centric enrichment analysis showed differential expression of genes associated with hepatic cholestasis, fibrosis, hepatitis, and hypercholesterolemia. Pertubations of genomic pathways also predicted that the PBDE mixture will be hepatocarcinogenic by nongenotoxic mechanisms. Genomic signature analysis indicated the PDBE transcriptome response is strongly similar to that of phenobarbital, which has been shown to cause liver and thyroid tumors in rats. Coexpression network analysis suggested that the transcription factors CAR, PXR, FOXA3, NRF2, and SREBPF1, as well as the bile salt transporter, NTCP, and the copper transporter, CTR1, play critical roles in PBDE toxicity. Pathway analysis confirmed the role of these genes and their related pathways in the global transcriptional response to PBDEs and further highlighted the role of FXR and LXR signaling. Overall, these data indicate that PBDEs elicit an integrated transcriptional response via perturbation of nuclear receptor, oxidative stress and sterol/cholesterol signaling pathways. Disruption of these pathways has the potential to induce carcinogenic responses in the liver and other organs. 1594 AGE AND SEX DIFFERENCES IN RENAL GENE EXPRESSION DURING THE RAT LIFE CYCLE. J. C. Kwekel, V. G. Desai, T. Han, W. S. Branham, C. L. Moland and J. C. Fuscoe. Systems Toxicology/Center for Functional Genomics, U.S. FDA/National Center for Toxicological Research, Jefferson, AR. Age- and sex-related susceptibility to adverse drug reactions is a key concern in understanding drug safety and disease progression. Age is a predisposing condition for susceptibility to adverse effects of some drugs. There is also evidence from the study of hepatic disease and cancer to suggest sexually dimorphic susceptibilities as well. We hypothesize that the underlying suite of genes expressed at various developmental and life-cycle stages will impact susceptibility to adverse drug reactions. Thus, understanding the natural expression patterns of genes throughout the life span of the rat surrogate model species in both sexes will inform our assessments of adverse drug reactions. The kidney plays a central role in the pharmacokinetics and excretion of drugs via key molecular transporters. Untreated, male and female F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age. Kidney tissues were collected for histology and gene expression analysis. Whole-genome rat microarrays (Agilent) were used to query global expression profiles. A 2-way ANOVA (p < 0.0001) along with 1.5 fold change in relative expression was used to identify 4,061 unique genes that were differentially expressed by sex or age. Principal component analyses (PCA) revealed notable expression profile differences between different age groups with greatest differences observed between 2 and 6 weeks of age. Adult and aging animal expression profiles clustered in a large group with 104 week animals showing slight divergence. PCA loadings analysis prioritized genes having the greatest influence in sex and age related differences in expression and included metabolism and transport genes Cyp1a1, Ugt2b3, Abcg5, Abcb11 and Abca8, among others. K-means cluster analysis identified groups of genes exhibiting similar lifecycle expression profiles. These results suggest specific groups of kidney genes that may underlie specific periods of susceptibility to adverse drug reactions.
1595 GENE EXPRESSION PROFILE OF RAT PRIMARY HEPATOCYTES EXPOSED TO DI(2-ETHYLHEXYL) PHTHALATE OR DIISONONYL PHTHALATE, THE PATH TO GENERATE TOXIGENOMICS DATA AS SUPPORT FOR STRUCTURE ACTIVITY RELATIONSHIPS ASSESSMENTS. J. M. Naciff, G. J. Overmann, R. Adams, G. J. Carr, J. P. Tiesman and G. P. Daston. Procter & Gamble, Cincinnati, OH. We have evaluated the transcriptional profile of rat primary hepatocytes elicited by Di(2-ethylhexyl) phthalate (DEHP) or Diisononyl phthalate (DINP) exposure, at two doses (250, and 1000 μM) and two time points (24 and 48 h), using the Rat Expression Array 230 2.0 (Affymetrix). This study is part of a project which ultimate goal is to determine whether gene expression profiles from cells in culture (liver-derived) can provide us with sufficient information to support the Structure Activity Relationships (SAR)-based assumptions about biological activity. The genomic response of the rat primary hepatocytes to either DEHP or DINP exposure is both dose- and time-dependent. Trend analysis indicated that the expression of more than 2770 and 1680 probe sets is modified (p ≤ 0.0001) by DEHP and DINP, respectively. Comparing the expression profile induced by DEHP versus the one induced by DINP, at equivalent exposure times, we clearly identified a relatively large number of genes (represented by 1164 unique probe sets) whose expression changes in the same direction by exposure to these two phthalates. The products encoded by these genes have been associated a great variety of biological processes and molecular functions, particularly enriched in lipid, fatty acid, glutathione and xenobiotic metabolic processes. Further, phthalate exposure results in changes in the expression of unique genes whose products are involved with cell cycle regulation, regulation of programmed cell death (apoptosis), and with stress response. The robustness of the response of the rat primary hepatocytes to these two phthalates indicates that the transcription profiling offers relevant biological data to support the SAR-based assumptions about biological activity, in this in vitro system. 1596 PERCELLOME TOXICOGENOMICS PROJECT AND ITS APPLICATION TO STUDIES ON ANTICANCER AGENTS. J. Kanno, K. Aisaki, K. Igarashi and S. Kitajima. Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, Tokyo, Japan. Sponsor: N. Ryoichi. Percellome Toxicogenomics Project has been launched to develop a comprehensive gene cascade database/informatics for the mechanism-based predictive toxicology. For this purpose, a normalization method designated as “Percellome” is developed (BMC Genomics 7:64, 2006) to generate mRNA expression values in “copy numbers per one cell” from microarrays and Q-PCR. Thus, data are directly compared among studies and even different organs. Up to now, the time- and dose-dependent alteration of gene expression induced by a single oral exposure in mouse liver and other organs (4 time points x 4 dose levels, triplicate, 48 per chemical) are studied on more than 100 chemicals. Transcriptomic data is expressed as 3-D graphs (time x dose x copies per cell); 45,000 surfaces corresponding to the probe sets of the Affymetrix Mouse Genome 430 2.0 Array. Here, we applied this comprehensive approach for the mechanisms/toxicity of some anticancer agents and related compounds. As a result, thalidomide and 5-FU share the same target(s) in liver and lung involving cdkn1a (p21). However, the time course of the induction of the key mRNA was different (2hr versus 24hr). Accordingly, the molecular networks were different; thalidomide seems to trigger direct signaling towards p21 (p53 network), whereas 5-FU seems to induce signaling towards p21 secondary to pyrimidine metabolism and protein synthesis failure. In addition, both thalidomide and 5-FU induce similar stress responses not only in liver and lung but also kidney and heart indicating possible toxicity to those organs as well. (Supported by Health Sciences Research Grants from the Ministry of Health, Labour and Welfare, Japan) 1597 COMPARISON OF BASAL AND CRVI-MEDIATED SOLUTE CARRIER GENE EXPRESSION IN RODENT DUODENAL EPITHELIUM. S. Kim 1 , C. M. Thompson 2 , A. K. Kopec 1 , M. A. Harris 2 and T. R. Zacharewski 1 . 1 Biochemistry & Molecular Biology and Center for Integrative Toxicology, East Lansing, MI and 2 ToxStrategies, Inc., Katy, TX. Hexavalent chromium (CrVI) is structurally similar to phosphate and sulfate ions and readily enters cells via anion transporters. Chronic administration of high doses of sodium dichromate dihydrate (SDD) leads to intestinal cancer in mice, but not in rats. To further evaluate species-specific differences in CrVI carcinogenicity, duodenal epithelia of female B6C3F1 mice and Fisher rats were examined after 7 days of continuous exposure to 0.3-520 mg/L SDD in drinking water. Whole genome 4x44K Agilent two-color oligonucleotide arrays identified basal expression of 289 unique solute carrier (SLC) transporter orthologs in control animals. SLC intensity values were normalized to the average signal intensity for all SLC orthologs. Overall, SLC expression levels were comparable between species with some notable exceptions. For example, there were species-specific differences (~86-20-fold) in the basal expression of SLC 35c1, 7a7, 6a20, 25a25, 5a11, 2a2, 25a4, 35d1, 25a25, and 35e2 in the mouse, while basal levels of SLC 25a4, 9a1, 30a3, 15a1, 44a4, 26a3, 4a4, 24a6, 35a4, and 39a8 were ~82-15-fold higher in the rat. Exposure to SDD differentially regulated 119 mouse and 48 rat SLC orthologs (|fold change|>1.5, P1(t)>0.999), of which 35 were commonly regulated in both species. The uptake of CrVI is believed to be mediated by Slc4a family, in agreement with high basal expression of Slc4a2 (3.5-fold) and Slc4a5 (2.1-fold) in the mouse, and Slc4a4 (13.4-fold) and Slc4a7 (21.3-fold) in the rat. SDD treatment did not affect expression of SLCs 4a2/5 in the mouse, but significantly repressed SLCs 4a4/7 in the rat at the highest doses. SLC4a1, the putative CrVI transporter, exhibited low basal expression and was not differentially regulated by SSD. The results suggest that CrVI exposure may alter SLC transporter expression. Differences in basal SLC expression and regulation could partially explain the observed carcinogenic phenotype differences between rats and mice. 1598 NOVEL SHORT TERM PREDICTION SYSTEM FOR CARCINOGENICITY OF CHEMICALS BY HEPATIC TRANSCRIPT PROFILING IN A 28-DAY REPEAT-DOSE TOXICITY STUDY. F. Saito 1 , H. Matsumoto 1 , M. Takeyoshi 1 , Y. Yakabe 1 and T. Shirai 2 . 1 Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute (CERI), Japan, Saitama, Japan and 2 Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Carcinogenicity is one of the most important endpoint of chemical safety for not only pharmaceutical compound but industrial chemicals. However, rodent tests for carcinogenicity of chemicals such as a traditional 2-year study, requires large number of animals and large amount of compounds. In this study, we have been trying to develop a highly accurate and wide applicable prediction method of chemical carcinogenicity with short term toxicity test up to 28 days. We analyzed the gene expression profiles in livers of Fischer 344 rats administered with 47 carcinogenic and 26 non-carcinogenic compounds as test data set. Gene expression of the livers were analysed using a custom oligo microarray, NEDO-ToxArray III and Affymetrix GeneChip®. Functions and networks analyses of up- or down-regulated genes were conducted using the Ingenuity Pathways Analysis (IPA) software. A prediction formula was developed by most plausible method using gene expression profiles of test data set with SVM approach. The established formula showed a concordance of 94.4% with test data set, and the formula was validated by application of 18 compounds as the training data with a concordance of 83.3%. Furthermore, gene expression data obtained from Sprague-Dawley rat treated with short-term toxicity test with known carcinogens and non-carcinogens were applied to the prediction formula, and all hepatic carcinogens and non-carcinogens were accurately predicted. In addition, key genes used in the prediction formula showed a common gene network contained tumor suppressor gene, p53 concerned with cell cycle, DNA repair, and apoptosis. Thus, we developed a promising short term prediction system for carcinogenicity of chemicals using gene expression profiles in livers of rats before neoplastic changes. 1599 TIME AND CONCENTRATION DEPENDENT REGULATION OF THE TRANSCRIPTOME AND THE PHENOTYPE OF A MOUSE LIVER CELL LINE EXPOSED TO BAP. D. Jannuzzi Madureira 1, 2 , J. Michaelson 3 , A. Beyer 3 , S. Trump 4 , I. Lehmann 4 and K. Schirmer 1, 2 . 1 Eawag, Swiss Federal Institute of Aquatic Science and Technology, Duebendorf, Switzerland, 2 Swiss Federal Institute of Technology Zürich, Switzerland, Zuerich, Switzerland, 3 Biotechnology Center TU Dresden, Dresden, Germany and 4 Helmholtz Centre for Environmental Research, Leipzig, Germany. Sponsor: M. R. Embry. The aim of the systems biology initiative, “From contaminant molecules to cellular response: system quantification and predictive model development”, is to build a model of interactions between cells and the toxic chemical Benzo-a-Pyrene (BaP). As part of this initiative, this project aims to identify the regulation of genes by BaP in a time and concentration-dependent manner and relate the regulation to cellular distribution of BaP and the physiologic or toxicologic cellular response. The well SOT 2011 ANNUAL MEETING 343
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIODEGRADABLE MATERIALS FOR TISSU
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that genetic toxicology data are ge
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well-orchestrated lung inflammation
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scribed in the literature. We have
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years ago). We will illustrate how
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involved in the biodegradation proc
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stem cells but rather a treatment i
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additional compound showed agreemen
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82 COMPARISON OF 3H-THYMIDINE INCOR
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irritants. While in practice these
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alleles are especially vulnerable t
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109 CD4+ T CELL INTRINSIC TNF RECEP
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118 TO STUDY THE SIGNAL TRANSDUCTIO
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PAHs, such as dioxins, are prevalen
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containing substituents and/or hydr
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146 COMPUTATIONAL MODELING FOR QT P
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suggest that the combination of too
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164 TRANSLOCATOR PROTEIN (18 KDA) (
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function as a metal binding protein
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laboratory has demonstrated that NR
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known. The aim of this study was to
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from 5 to 28 days in duration) in e
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positive cells, caspase-3 activatio
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creased level in the 46 kDa preproe
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invasiveness at concentrations repr
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thracene (DMBA,50 μg in acetone, a
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247 CO-CARCINOGENESIS OF N, N- DIET
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sponds to the endosomal dsRNA that
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ODD in both WT (maximum 177% of con
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Lastly, using p53siRNA cells, p53 w
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its receptor Mpl to exert its funct
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294 LOW LEVEL OF LEAD CAN INDUCE PH
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lunar surface presented potential h
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lar about cellular export mechanism
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DNA in the kidney medulla, grandula
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5.00 and 7.50 mg/kg/day by oral gav
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events and carcinogenesis. Here we
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tinization of cells of the hair fol
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358 CHARACTERIZATION OF GENOME-WIDE
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RNAi were also performed to identif
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376 A FUNCTIONAL CROSSTALK BETWEEN
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UGT1A gene induction, while this re
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tivity, specifically peroxisome pro
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and cytotoxic effects; however, its
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histone deacetylase that is necessa
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ment. Paradoxically, buthionine sul
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drug leflunomide and its major (A77
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442 GENE EXPRESSION AND MORPHOLOGIC
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451 INHIBITION OF THE MITOCHONDRIAL
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460 SULFORAPHANE PREVENTS ACETAMINO
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drophilic/lipophilic balance. Other
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pharmacokinetic and toxicological p
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489 USE OF ‘OMICS DATA TO IMPROVE
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498 APPLICATION OF AGE-SPECIFIC ADJ
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507 A DOSE VOLUME TOLERABILITY STUD
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involved the use of an acute inflam
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sorption in the gastrointestinal (G
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(ABC) transporters actively transpo
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545 BEHAVIORAL EFFECTS OF REPIN IN
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a blood pressure phenotype that res
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and inhalation exposure system that
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and lethality associated with these
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position, on vascular reactivity an
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therefore more accurate and reprodu
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commercial chrysotile product that
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elative to their controls. ST-depre
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ats. The majority of the studies fo
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in the China Jintan Child Cohort St
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corneum thickness, cellular epiderm
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645 EVALUATION OF THE IN VITRO EPIS
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654 TCDD ADSORBED ONTO NATURAL AND
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tion revealed no test article-relat
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671 INFLAMMATION AND TISSUE DAMAGE
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model, ethanol was found to inhibit
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689 ENHANCED SUPPRESSIVE FUNCTION O
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NAC + LPS yielded different levels
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707 LIFE-STAGE PBPK MODELS FOR MULT
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downstream of the apical endpoint o
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726 UPDATED ALUMINUM PHARMACOKINETI
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global parameter sensitivity analys
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and renal inflammation induced by 2
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754 PLASMA, URINE, AND TISSUE CONCE
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cently characterized transporter OA
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exposure system was developed from
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lood cell mass and decrease in urin
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practical alternatives to MC in non
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imals dosed with 167 mg/kg THU alon
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and organ weights, clinical signs a
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yet is induced in most bladder and
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830 RISK ASSESSMENT OF THE SPILL: C
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knowledgebase creation. Results are
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852 UNDERSTANDING STRUCTURAL AND PH
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for integrating epidemiology and an
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motor activity, including age of th
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y partial purification of urine (fr
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pacity for self-renewal and may dif
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sue. The depth of our analysis led
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910 IMPLEMENTING CALIFORNIA’S GRE
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concentrations in six tissues and b
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934 THE FDA’S LIVER TOXICITY KNOW
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943 GENOME-WIDE DNA METHYLATION DIF
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membrane localization and subsequen
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trols, respectively. Subtoxic and t
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survival using both smoking regimes
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as non-, weak, moderate, or strong
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988 NNK-INDUCED CYTOKINE ALTERATION
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group (one-way ANOVA, p90 % viabili
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ered as an organ involved in xenobi
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Transport of CPZ across the Caco-2
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estrous cycle and sexual behavior d
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mRNA expression levels. Collectivel
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1043 THE EFFECTS OF ENDOCRINE DISRU
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1052 MONO-2-ETHYLHEXYL PHTHALATE IN
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Results: MC was variable within and
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UtSMCs. Phosphorylation of FoxO1 wa
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nonpregnant and pregnant diabetic m
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1089 PFOA-INDUCED LIVER EFFECTS IN
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events in the liver. AZD9056 was ev
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The peppermint oil caused a concent
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OA did not affect food consumption.
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1126 PERSISTENT DEVELOPMENTAL ARYLH
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1135 BACH2 BINDING TO Prdm1 AS A ME
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The purpose of this project was to
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one marrow. Since Chk1 is an attrac
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1163 THE MRNA AND MIRNA PROFILE OF
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have now compared the IC50 values b
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1181 ELUCIDATION OF FACTORS DETERMI
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enced by pre-exposure to cigarette
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if abnormal PF was associated with
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weight (P=0.016) and small for gest
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portant cause of death, compared to
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posure groups. However, the differe
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Naphthalene is routinely analyzed i
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1245 SEASONAL CHARACTERIZATION OF H
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1255 URINARY T, T MUCONIC ACID LEVE
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modating a reliable data evaluation
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enzoquinone generate ROS and arylat
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teins (e.g. C3, 4, and 5, APOB, VDB
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1293 TRANSFORMING GROWTH FACTOR BET
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mation was decreased to the same le
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1312 EVALUATION OF THE SENSITIVITY
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luted OFR and CRL. Culture media ex
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urinary TCPy levels, blood and brai
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activity. The dose-response curves
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mice, each with 4 dose groups. One
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Page 373 and 374: those with high nickel content are
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cyanoacetic acid increased 2-3 fold
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1845 IS THE PROMISCUITY OF THE ARYL
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crorarray analysis. RT-PCR results
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are a family of phase-II biotransfo
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ous labs. As a result of positive s
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down the doses may produce more tox
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spectively. Below 100 mg/l of gemfi
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1900 GENERATION OF PRECISION CUT LI
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iomarkers or observation of lesions
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creased reticulocytes and lymphocyt
Page 417 and 418:
statistically significant interacti
Page 419 and 420:
monize sample preparation and analy
Page 421 and 422:
NPC and sinonasal cancer in neighbo
Page 423 and 424:
showed incidences of lung and nasal
Page 425 and 426:
utylbenzenes, exhibited most simila
Page 427 and 428:
1975 DIFFERENTIAL MODULATION OF CYP
Page 429 and 430:
organic As to MMA(V) and a lower ca
Page 431 and 432:
ole in invasion and metastasis of c
Page 433 and 434:
3T3-L1 cells to low-levels of arsen
Page 435 and 436:
2011 IDENTIFICATION OF A NOVEL VX M
Page 437 and 438:
This work was supported by Cooperat
Page 439 and 440:
2029 EFFICACY OF ENDOTRACHEAL ADMIN
Page 441 and 442:
Diazepam injections and its combina
Page 443 and 444:
2047 ESTERASE ACTIVITIES AND HEMOST
Page 445 and 446:
nanoparticle-induced toxicity progr
Page 447 and 448:
house, were iv infused into rats ov
Page 449 and 450:
een explored. This study investigat
Page 451 and 452:
croscopic analysis revealed that on
Page 453 and 454:
egg yolk collected from turtles inh
Page 455 and 456:
consistency of results in both expe
Page 457 and 458:
2111 CYTOCHROME P450 3A5 GENOTYPE I
Page 459 and 460:
esidues of organophosphates or thei
Page 461 and 462:
manganism. Recent work from our lab
Page 463 and 464:
Aβ1-40 in CSF and hippocampus in P
Page 465 and 466:
2147 CATALASE MANIPULATIONS MODIFY
Page 467 and 468:
ation based on real-world exposure
Page 469 and 470:
NPs. Aggregation of citrate-stabili
Page 471 and 472:
2175 THE ROLE OF SURFACE CHEMISTRY
Page 473 and 474:
seen rapid uptake in biological ima
Page 475 and 476:
effect on uterine weight or vaginal
Page 477 and 478:
dicating widespread exposure. While
Page 479 and 480:
components into the liver parenchym
Page 481 and 482:
2223 ISOLATION AND DETECTION OF RIC
Page 483 and 484:
stored (-20 celsius degree). The co
Page 485 and 486:
2241 DDA, A BIOMARKER FOR ENVIRONME
Page 487 and 488:
2249 INTERACTION BETWEEN DIETARY SE
Page 489 and 490:
2258 PHARMACOKINETICS, EXCRETION BA
Page 491 and 492:
2267 SENSITIVE AND SPECIFIC FLUORES
Page 493 and 494:
2276 METABOLISM AND DISPOSITION OF
Page 495 and 496:
ment of hypertension in companion a
Page 497 and 498:
for the propyl series can be used f
Page 499 and 500:
2304 IN VITRO EXPOSURE AND EVALUATI
Page 501 and 502:
2313 THE SYNERGISTIC EFFECT OF SODI
Page 503 and 504:
genes that play a crucial role in M
Page 505 and 506:
2330 THE ROLE OF TRANSFORMING GROWT
Page 507 and 508:
ined following up to 96 h continuou
Page 509 and 510:
effect doses obtained with the rat
Page 511 and 512:
diated transcriptional response of
Page 513 and 514:
docrine disruptor activities of EDC
Page 515 and 516:
individuals. Week 6 results were qu
Page 517 and 518:
functionality of photosystem II and
Page 519 and 520:
wild mice (Mus musculus) from areas
Page 521 and 522:
2406 TOXICITY AND BIOACCUMULATION O
Page 523 and 524:
Isocitric acid is the acid in the h
Page 525 and 526:
2425 EFFECTS OF FUMONISINS IN ETHAN
Page 527 and 528:
centration(μg/g) were: 5.1-95.3; 2
Page 529 and 530:
2445 AUTOPHAGY IN DEVELOPMENT: A LI
Page 531 and 532:
sures to inhaled Mn in dust. Nevert
Page 533 and 534:
2466 CRITICAL EVALUATION OF ANIMAL
Page 535 and 536:
elationships predict that resting r
Page 537 and 538:
2489 COMPARATIVE TOXICITY OF BIODIE
Page 539 and 540:
2497 TRANSCRIPTIONAL REGULATION OF
Page 541 and 542:
2506 TOXICOLOGICAL CONSIDERATIONS O
Page 543 and 544:
launched with the aim of developing
Page 545 and 546:
forms mRNA expression levels were a
Page 547 and 548:
2534 CUTANEOUS WOUND HEALING IN THE
Page 549 and 550:
wells (0, 1, 5, 10, 25, 50, 100, an
Page 551 and 552:
2553 AN ORGANOTYPIC MICROLIVER PLAT
Page 553 and 554:
serum-free media. At 24 hrs, the gr
Page 555 and 556:
2572 INCREASED ARSENIC BIOACCESSIBI
Page 557 and 558:
nology to develop improved methods.
Page 559 and 560:
tuna, swordfish, or mako shark (3.5
Page 561 and 562:
nificantly reduce circulating thyro
Page 563 and 564:
grouped into 9 observation periods
Page 565 and 566:
histopathological or biochemical ev
Page 567 and 568:
exhibited a hyperactive phenotype,
Page 569 and 570:
the search of effective drugs for e
Page 571 and 572:
2644 COVALENT BINDING OF 14 C 2-MET
Page 573 and 574:
aries targeting all transcription f
Page 575 and 576:
(p 9 weeks) and CSC phenotype acqui
Page 577 and 578:
2673 IMMUNE-MEDIATED VASCULAR INJUR
Page 579 and 580:
for risk identification and charact
Page 581 and 582:
to control toxicant delivery in tob
Page 583 and 584:
Author Index (Continued) The numera
Page 585 and 586:
Page 587 and 588:
Page 589 and 590:
Page 591 and 592:
Page 593 and 594:
Page 595 and 596:
Page 597 and 598:
Page 599 and 600:
Page 601 and 602:
Page 603 and 604:
Page 605 and 606:
Page 607 and 608:
Page 609 and 610:
Page 611 and 612:
Keyword Index (Continued) Arsenite
Page 613 and 614:
Keyword Index (Continued) Covalent
Page 615 and 616:
Keyword Index (Continued) flow cyto
Page 617 and 618:
Keyword Index (Continued) innate im
Page 619 and 620:
Keyword Index (Continued) nanoparti
Page 621 and 622:
Keyword Index (Continued) preservat
Page 623 and 624:
Keyword Index (Continued) Thrombocy
Page 625 and 626:
Toxicological Sciences The Official
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