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and the percentage of responders per group was determined. The percentage of responders ranged from 80-100 and 0-20 for the positive (ofloxacin, amoxicillin, sulfamethoxazole) and negative (metformin, acetaminophen, phenobarbital) control drugs, respectively, indicating that the model is able to differentiate between positive and negative controls. These data suggest that this model may be a useful tool for identifying compounds with the potential to produce hypersensitivity responses. 1498 HLA-SPECIFIC T-CELL ACTIVATION AS AN UNDERLYING CAUSE OF DRUG-INDUCED HYPERSENSITIVITY. J. M. Goodwin 1 , T. Kawabata 2 and M. T. Pletcher 1 . 1 Compound Safety Prediction, Pfizer, Groton, CT and 2 Immunotoxicology CoE, Pfizer, Groton, CT. Drug hypersensitivity is a major safety issue in drug discovery. Though it occurs in only a small fraction of the patient population, the results are often severe. Genome-wide association studies have been employed to better understand the underlying mechanisms and have shown an association between alleles of the major histocompatibility complex (MHC) region and an individual’s hypersensitivity to certain drugs. One hypothesis that has been put forth to explain the genetic relationship between adverse events and the MHC is the Pharmacological Interactions (PI) concept. It states that certain drugs can bind to T-cell receptors, mimicking a ligand, resulting in T-cell activation in an MHC-dependent fashion. We sought to further investigate the validity of this hypothesis by determining a transcriptional response indicating T-cell activation in PBMCs with hypersensitive haplotypes. PBMCs with known reactive and non-reactive MHC haplotypes were dosed with their corresponding reactive drugs (HLA-B*5701 with Abacavir and HLA-B*1502 with Carbamazepine) and RNA was profiled on microarrays covering 172 genes associated with T and B cell activation. We identified 27 candidate genes, including IL-12beta, CD80, IL-7, IL-13, CXCR3, and CSF2, whose expression was altered only in the hypersensitive haplotype treated with reactive drug. We then examined the expression changes of these selected genes on a larger panel of PBMCs from patients with various non-reactive and reactive haplotypes to confirm the transcriptional fingerprint. In conclusion, we have identified a set of genes that are regulated in an MHC-dependent fashion in PBMCs treated with compounds known to induce hypersensitivity reactions in patients carrying these specific alleles. This identification of the genetic and transcriptional factors involved in the development of immune-mediated idiosyncratic tissue injury provides the insight necessary to develop diagnostic tools to identify patient populations at increased risk and new treatment strategies. 1499 EARLY CHANGES IN AROMATIC AMINE-INDUCED IDIOSYNCRATIC DRUG REACTIONS. W. Ng and J. Uetrecht. Pharmacy, University of Toronto, Toronto, ON, Canada. Virtually all drugs that contain a primary aromatic amine group are associated with a high incidence of idiosyncratic drug reactions (IDRs) and this is considered a structural alert for drug development. This suggests that this functional group has biological effects that might be used as a biomarker to predict IDR risk as well as provide clues to the mechanism of IDRs. A previous microarray study to determine the early changes (12 h) in hepatic gene expression in Brown Norway rats treated with the aromatic amine drugs sulfamethoxazole (SMX, 150 mg/kg), dapsone (DDS, 20 mg/kg), and aminoglutethimide (AMG, 80 mg/kg) provided the basis for our present studies. The pattern of mRNA changes was significantly different for the 3 drugs. Three distinct changes from the microarray data were pursued in terms of their downstream effects: early insulin-induced gene (Eiih), chemokine (C-X-C) 1 (Cxcl1), and genes involved with the Nrf2-ARE pathway. PCR analysis of Eiih confirmed that it was up-regulated at 12 h in the liver with all drugs tested, although the change was greater for AMG and DDS than SMX. The function of Eiih is presently unknown but these data suggest that it could be a potential biomarker of aromatic amine-induced IDRs. Despite moderate changes in hepatic Cxcl1 and an up-regulation of Cxcl1 protein levels in the blood of AMG-treated rats this was not the case for SMX- or DDS-treated animals. This increase in Cxcl1 coincided with a transient increase in peripheral blood neutrophils 24 h after AMG treatment. This finding may be related to the agranulocytosis that sometimes occurs in AMG-treated patients. Up-regulation of the Nrf2-ARE pathway was also observed: increased glutathione-S-transferase and thioredoxin reductase in the liver 48 h after AMG treatment. This suggests that these aromatic amines induce oxidative stress. These results demonstrate the diverse effects of aromatic amine drugs and illustrate the difficulties in finding a common biomarker that predicts IDR risk. This research was funded by grants from the Canadian Institutes for Health Research. 322 SOT 2011 ANNUAL MEETING 1500 THE USE OF MAST CELLS DERIVED FROM HUMAN CD34+ HEMATOPOIETIC STEM CELLS AS A TOOL FOR PREDICTING PSEUDOALLERGIC DRUG REACTIONS. J. Whritenour 1 , C. Homiski 1 , K. Haskell 2 , M. Thiede 2 and T. T. Kawabata 1 . 1 Immunotoxicology CoE, Drug Safety Research and Development, Pfizer, Inc., Groton, CT and 2 Genetically Modified Mice CoE, Pfizer, Inc., Groton, CT. Pseudoallergic (anaphylactoid) reactions are the result of direct mast cell activation and degranulation via an IgE-independent mechanism, resulting in the release of specific mediators such as histamine, tryptase, and cytokines. Assays to predict the potential of drugs to produce pseudoallergic reactions in humans are currently unavailable but would be a useful tool during drug development. In this study, we explored the utility of CD34+ hematopoietic stem cell (HSC)-derived mast cells for predicting the pseudoallergic potential of various drugs using histamine release as an indicator of mast cell degranulation. CD34+ HSC from human bone marrow donors were cultured over a period of ~68 days with various cytokines and differentiated into cells expressing a mast cell phenotype (FcεR1+, CD45+, CD117+). Mast cells were plated (5x10 4 cells/well) and incubated for 30 min, 60 min, or 24 hr with either vehicle (PBS), or compounds known (tubocurarine, morphine) or not (metformin, acetaminophen) to produce pseudoallergic reactions in humans. Following incubation, contents from each well were centrifuged to remove the cells and the supernatants were collected and analyzed for histamine content using a commercially available ELISA kit. While the overall magnitude of the histamine response appears to be donor-dependent, CD34+ HSC-derived mast cells consistently responded to the known pseudoallergens. Histamine levels were similar between cells treated with the negative controls and the vehicle. No significant differences were measured in the quantity of histamine released when mast cells were incubated with compounds for 30 min, 60 min, or 24 hr. These data indicate that human CD34+ HSC-derived mast cells may be used to predict for pseudoallergic potential of drug development candidates. 1501 EFFECT OF RETINOIC ACID ON NEVIRAPINE- INDUCED SKIN RASH AND THE INVOLVEMENT OF TH17 CELLS. X. Chen and J. P. Uetrecht. Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada. Introduction: Nevirapine (NVP) is used to treat AIDS but is associated with a high incidence of skin rash and liver toxicity. We found that it also causes a similar skin rash in the Brown Norway (BN) rats. The NVP-induced skin rash in BN rats is clearly immune-mediated and we think the mechanism is similar to that in humans. For example, a low CD4 + T cell count decreases the risk of rash in both rats and humans. Furthermore, CD4 + T cells can transfer the sensitivity from sensitized animals to naïve animals. We found that IL-17 was produced by lymphocytes from NVP-sensitized animals suggesting that IL-17 and/or Th17 cells might be involved in the pathogenesis. Retinoic acid (RA), a vitamin A metabolite, is reported to inhibit Th17 cells. In this preliminary study we examined the effect of RA on NVPinduced skin rash and the involvement of Th17 cells. Methods and Results: Female BN rats co-treated with NVP and RA for 21 days had no symptoms of NVP-induced idiosyncratic reactions, i.e. red ears and/or skin rash. However, slightly lower plasma levels of NVP and/or its metabolites were observed. In the peripheral blood, NVP treatment significantly decreased the percentage of cells that express CD4 + /CD161 low , which in humans is the precursor of Th17 cells. We also observed a big spike of CD4 - CD161 low cells on day 4 following NVP treatment but they deceased to baseline levels in 1 week. These might be CD8 + or NK cells and they need to be further characterized. Conclusions: The protective role of RA on NVP-induced skin rash might be a result of decreased drug plasma levels. However, this needs to be confirmed by using a higher dose of NVP or a P450 inhibitor with co-administration of RA. The involvement of Th17 cells (CD4 + IL17 + ) will also be investigated using a more direct method, i.e. intracellular staining. Completion of these studies will provide a better understanding of the mechanism of NVP-induced skin rash and, in turn, this may provide possible ways to prevent and/or treat idiosyncratic drug reactions. This work was supported by grants from CIHR.
1502 IMMUNOLOGICAL ASPECTS OF AN ANIMAL MODEL OF AMODIAQUINE-INDUCED LIVER TOXICITY. J. Li 1 , H. C. Workman 2 , P. Cai 3 , G. Kourteva 4 , H. Hilton 4 , H. Haggerty 1 , D. Moore 2 and J. Uetrecht 3, 5 . 1 Immunotoxicology, Bristol-Myers Squibb Company, New Brunswick, NJ, 2 Nonclinical Safety, F. Hoffmann-La Roche Inc., Nutley, NJ, 3 Pharmacy, University of Toronto, Toronto, ON, Canada, 4 TRS-RNA Biomarker Technology, F. Hoffmann-La Roche Inc., Nutley, NJ and 5 Medicine, University of Toronto, Toronto, ON, Canada. Rationale: As in humans, amodiaquine (AQ) causes a delayed onset liver injury in rats, but the ALT returns to normal despite continued treatment. This is consistent with immune tolerance and we tried to overcome this tolerance with IL-7 co-treatment. Experimental Procedures: Male Brown Norway rats were treated with AQ at 62.5 mg/kg/day p.o. for six weeks with IL-7 co-treatment at 100 ug/kg/day i.p. for 7 days during either the 2nd or 3rd week. Serum ALT and cytokines were measured weekly. Liver histopathology, splenocyte phenotype, hepatic mRNA expression, serum prolactin and serum microRNAs were determined at the end. Results: Liver findings include individually scattered activated Kupffer cells (KC) (vacuolated and clustered) and KC microgranulomas as well as hepatocyte single cell necrosis. This was slightly enhanced by both IL-7 co-treatment schedules. Macrophage and B cell activation was observed in the spleen. IL-7 given during the 3rd week appeared to increase the elevation of ALT while IL-7 during the 2nd week delayed it. There was a good correlation between serum levels of ALT and MCP-1. Hepatic mRNAs involved in apoptosis (i.e. caspase 1, Fas and Faslg) and immunological functions (i.e. CD3, IL-4, IL-18, CCL5, TLR 2, 4, 7) were up-regulated in all AQ groups, with prolactin receptor being most up-regulated (40-60 fold, p < 0.0001). IL-7 co-treatment caused more gene expression changes (i.e. TNF-α, IL-1β). Significantly elevated serum levels of prolactin and microRNA-122 were also detected in AQtreated rats. Conclusions: Amodiaquine treatment for 6 weeks resulted in KC hyperplasia and single cell necrosis in the liver. The delayed onset and up-regulation of immune-related genes suggests that this injury is immune-mediated. This work was supported by CIHR grants and the Roche postdoctoral fellowship program. 1503 CHANGES IN HEPATIC GENE EXPRESSION INDUCED BY AMODIAQUINE IN RATS. J. Uetrecht 3, 5 , J. Li 1 , G. Kourteva 2 , H. Hilton 2 , P. Cai 3 , H. C. Workman 4 , H. Haggerty 1 and D. Moore 4 . 1 Immunotoxicology, Bristol-Myers Squibb Company, New Brunswick, NJ, 2 TRS-RNA Biomarker Technology, F. Hoffmann-La Roche Inc., Nutley, NJ, 3 Pharmacy, University of Toronto, Toronto, ON, Canada, 4 Nonclinical Safety, F. Hoffmann-La Roche Inc., Nutley, NJ and 5 Medicine, University of Toronto, Toronto, ON, Canada. Rationale: Previous studies indicated that treatment of Brown Norway (BN) rats with amodiaquine (AQ) leads to activation of the immune system, especially in the liver. This study profiled changes in hepatic mRNA expression induced by AQ at early time points during the initiation of hepatotoxicity. Methods: (1) Male BN rats (n=4) were treated with AQ at 62.5 mg/kg/day p.o. for 7 days and hepatic mRNA expression related to apoptosis and immune activation was determined by qPCR array. (2) Male BN rats (n=4) were given a single dose of AQ at 200 mg/kg p.o. and global gene expression profile in the liver at 6 h was determined by an Affymetrix chip (rat genome 230 2.0). mRNA expression data were further analyzed by either on-line software for qPCR array or Partek for Affymetrix chip. Serum HMGB1 was also measured by ELISA. Results: AQ treatment for 7 days resulted in the up-regulation of several genes crucial for apoptosis such as Faslg, Bax, and Caspase 1 etc., and of immune-related genes such as CD2, CD3, IL-1b, IL-4, IL-18, CCL5, IFNg, and TLR 2 etc. Although not significant between groups, prolactin receptor (prlr) was dramatically up-regulated in two AQ-treated rats. Global gene expression screening at 6 h identified only a few but interesting changes: Prlr (2.6-fold, p
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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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Page 287 and 288: luted OFR and CRL. Culture media ex
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Page 295 and 296: exposure to both ATR and DACT has a
Page 297 and 298: third tetratricopeptide repeats (TP
Page 299 and 300: 7d. 28d after TMT injury there was
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Page 307 and 308: vated only in high-dose-treated ani
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Page 373 and 374: those with high nickel content are
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model of APAP metabolism and glutat
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logically & morphologically similar
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posure, blood chemistry was analyze
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elated to oxidative stress by measu
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ostasis), but work is needed to tra
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tokine products during carcinogenes
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ways as chemical stressors and, the
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toxicity of nanomaterials relates s
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1815 MEASURING COMPOUND SELECTIVITY
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1825 EFFECTS OF METABOLISM BY INTES
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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
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statistically significant interacti
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monize sample preparation and analy
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NPC and sinonasal cancer in neighbo
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showed incidences of lung and nasal
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utylbenzenes, exhibited most simila
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1975 DIFFERENTIAL MODULATION OF CYP
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organic As to MMA(V) and a lower ca
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ole in invasion and metastasis of c
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3T3-L1 cells to low-levels of arsen
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2011 IDENTIFICATION OF A NOVEL VX M
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This work was supported by Cooperat
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2029 EFFICACY OF ENDOTRACHEAL ADMIN
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Diazepam injections and its combina
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2047 ESTERASE ACTIVITIES AND HEMOST
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nanoparticle-induced toxicity progr
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house, were iv infused into rats ov
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een explored. This study investigat
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croscopic analysis revealed that on
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egg yolk collected from turtles inh
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consistency of results in both expe
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2111 CYTOCHROME P450 3A5 GENOTYPE I
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esidues of organophosphates or thei
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manganism. Recent work from our lab
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Aβ1-40 in CSF and hippocampus in P
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2147 CATALASE MANIPULATIONS MODIFY
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ation based on real-world exposure
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NPs. Aggregation of citrate-stabili
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2175 THE ROLE OF SURFACE CHEMISTRY
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seen rapid uptake in biological ima
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effect on uterine weight or vaginal
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dicating widespread exposure. While
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components into the liver parenchym
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2223 ISOLATION AND DETECTION OF RIC
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stored (-20 celsius degree). The co
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2241 DDA, A BIOMARKER FOR ENVIRONME
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2249 INTERACTION BETWEEN DIETARY SE
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2258 PHARMACOKINETICS, EXCRETION BA
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2267 SENSITIVE AND SPECIFIC FLUORES
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2276 METABOLISM AND DISPOSITION OF
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ment of hypertension in companion a
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for the propyl series can be used f
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2304 IN VITRO EXPOSURE AND EVALUATI
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2313 THE SYNERGISTIC EFFECT OF SODI
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genes that play a crucial role in M
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2330 THE ROLE OF TRANSFORMING GROWT
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ined following up to 96 h continuou
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effect doses obtained with the rat
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diated transcriptional response of
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docrine disruptor activities of EDC
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individuals. Week 6 results were qu
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functionality of photosystem II and
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wild mice (Mus musculus) from areas
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2406 TOXICITY AND BIOACCUMULATION O
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Isocitric acid is the acid in the h
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2425 EFFECTS OF FUMONISINS IN ETHAN
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centration(μg/g) were: 5.1-95.3; 2
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2445 AUTOPHAGY IN DEVELOPMENT: A LI
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sures to inhaled Mn in dust. Nevert
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2466 CRITICAL EVALUATION OF ANIMAL
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elationships predict that resting r
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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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The Toxicologist - Society of Toxicology

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