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1380 IN VIVO OPTICAL VISUALIZATION OF DOSE- DEPENDENT PATHOPHYSIOLOGY INDUCED BY INTRANASAL CADMIUM EXPOSURE IN THE MOUSE OLFACTORY SYSTEM. L. Czarnecki, A. H. Moberly, J. Pottackal, D. J. Turkel, T. Rubinstein and J. P. McGann. Psychology Department, Rutgers University, Piscataway, NJ. Intranasal exposure to cadmium has been related to olfactory dysfunction in humans and to nasal epithelial damage and altered odorant-guided behavior in rodent models. The pathophysiology, neural pathology, and perceptual deficits underlying these changes have not been fully elucidated. Transgenic mice expressing the fluorescent exocytosis indicator synatopHluorin (spH) in olfactory receptor neuron terminals (Bozza et al. 2004, Neuron, 9-21) received a unilateral intranasal instillation of 0.2 to 20 μg cadmium chloride and a contralateral vehicle instillation. Mass spectrometry demonstrated transport of this cadmium to the ipsilateral olfactory bulb. Mice were anesthetized, implanted with a cranial window overlying the olfactory bulbs, and odorant-evoked transmitter release from the olfactory nerve was quantified bilaterally via optical imaging of spH signals. Acute intranasal cadmium exposure reduces this odorant-evoked response from the olfactory nerve by up to 65% in a dose-dependent manner. Axonal projections from the olfactory epithelium to the olfactory bulbs were quantified in horizontal sections containing both bulbs. Cadmium exposure reduced the density of these projections by 20% at the highest dose of cadmium, consistent with histologically identified changes in the olfactory epithelium. In a behavioral psychophysical task, mice were trained to sample from an odor port and make a response when they detected an odorant against a background of room air. After bilateral intranasal cadmium instillations, mice were severely impaired in their ability to detect the target odor. This use of functional imaging of olfactory receptor neurons exposed to the toxicant serves a proof of concept that optical imaging in the olfactory system can permit the direct observation of exposure-induced pathophysiology in vivo. This approach is potentially useful in exploring the effects of any putative neurotoxicant that can be delivered intranasally. 1381 PERIPHERAL CADMIUM EXPOSURE INDUCES SECONDARY PATHOLOGY IN DOWNSTREAM BRAIN REGIONS IN THE MOUSE OLFACTORY SYSTEM. J. Pottackal, D. J. Turkel, T. Rubinstein, M. D. Kass, L. Czarnecki and J. P. McGann. Psychology Department, Rutgers University, Piscataway, NJ. The mammalian olfactory system is highly plastic, including central olfactory structures. This plasticity may be important to understanding the effects of inhaled toxicants because pathological changes in neurophysiology or neurochemistry of the brain may occur indirectly in response to a toxicant’s primary effects. We have previously demonstrated that acute intranasal instillation of cadmium chloride causes a profound reduction in odorant-evoked transmitter release from the olfactory nerve into the brain’s olfactory bulb, a deficit that persists for at least four weeks. Here we used immunohistochemical methods to document corresponding changes in the neurochemistry of olfactory bulb neurons that receive synaptic input from the olfactory nerve. Mice received unilateral intranasal instillations of 20 μg cadmium chloride and were sacrificed by intracardial perfusion 2 to 28 days later. Horizontal sections containing both olfactory bulbs were labeled by fluorescence immunohistochemistry for tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine production, or calbindin-d28k (CBD), an intracellular calcium-binding protein, and counterstained with DAPI. At two weeks post-exposure, but not earlier time points, periglomerular interneurons in the olfactory bulb exhibited a significant reduction in TH expression in sections from bulbs on the cadmium-exposed side compared to the contralateral bulb in the same section. This downregulation became more pronounced with time, reaching 50% by the 28 day time point. Unilateral naris occlusion mimicked this effect of cadmium-exposure, suggesting that the downregulation was caused by the reduction in sensory input rather than by cadmium intoxication per se. CBD levels were slightly elevated from 14-28 days, which could not be mimicked by naris occlusion. These data demonstrate that peripheral toxicant exposure can produce long-term secondary pathologies in downstream brain regions. Mere reversal of the peripheral damage may thus be insufficient to restore normal neural function. 1382 FAILURE TO REGENERATE OLFACTORY NERVE FUNCTION AFTER ACUTE INTRANASAL CADMIUM EXPOSURE IN THE MOUSE. T. Rubinstein, L. Czarnecki, D. J. Turkel, J. Pottackal and J. P. McGann. Psychology Department, Rutgers University, Piscataway, NJ. The mammalian olfactory epithelium undergoes a constant cycle of cell death and neurogenesis, such that the life span of a single olfactory receptor neuron is about four weeks. Here we report that olfactory pathophysiology following acute in- 296 SOT 2011 ANNUAL MEETING tranasal cadmium exposure does not recover over the succeeding month, as would be expected, but actually worsens over time. Transgenic mice expressing the fluorescent exocytosis indicator synatopHluorin (spH) in olfactory receptor neuron terminals (Bozza et al. 2004, Neuron, 9-21) received a unilateral intranasal instillation of 20 μg cadmium chloride and a contralateral vehicle instillation. After 2 to 28 days, mice were anesthetized, implanted with a cranial window overlying the olfactory bulbs, and odorant-evoked transmitter release from the olfactory nerve was quantified bilaterally via optical imaging of spH signals. Odorant-evoked release from the olfactory nerve on the cadmium-exposed side declined significantly over time, from approximately 35% of control two days after exposure to about 10% of control over the succeeding four weeks. Axonal projections from the olfactory epithelium to the olfactory bulb were quantified by measuring the optical density of spH expression (serving as an indicator of olfactory marker protein expression) in horizontal sections containing both olfactory bulbs. This labeling was reduced to 80% of control levels two days after cadmium exposure, and then declined significantly to about 40% of control over the succeeding four weeks. The persistence of olfactory nerve pathophysiology following intranasal cadmium exposure is unexpected in this regenerating system, and the steady deterioration of the neuronal responses is consistent with a failure to replace receptor neurons as they turn over. This suggests that cadmium may impair neuronal proliferation in the nasal epithelium. 1383 THE EFFECT OF TUNGSTEN ALLOY SURROGATES ON PC12 CELL GENE EXPRESSION. V. H. Adams 1 , D. I. Bannon 1 , M. G. Stockelman 2 and V. P. Mokashi 2 . 1 Army Institute of Public Health, U.S. Army Public Health Command (Prov), Aberdeen Proving Ground-EA, MD and 2 Naval Medical Research Unit, Dayton (NAMRU- Dayton), Wright-Patterson Air Force Base, OH. The neurotoxicity of metals such as tungsten (W), nickel (Ni), and cobalt (Co) has not been examined in detail. Moreover, the combined effect (whether additive, synergistic or neither) of these metals in a mixture is even less understood. Prior data indicate that deposition of radiolabeled tungstate (Na 2 188 WO4 ) in the brain is not accomplished through direct transport mechanisms along the olfactory nerves; however, investigators have reported that tungsten can be detected in rat brain following intravenous or intraperitoneal injection and oral gavage. As an alternative to in vivo testing, we used the PC12 cell in vitro model to explore the transcriptional profile of cells exposed to a tungsten alloy containing W, Ni and Co. Since W alloy becomes bioavailable during exposure, the ionic forms of the metals (WO 4 - , Ni +2 , Co +2 ) were used as an alloy surrogate. Based on Inductively Coupled Plasma – Mass Spectrometry analysis of tungsten alloy pellets incubated in PC12 cell tissue culture medium, the ratio of 3:2:1 mg/L (equivalent to 16, 34, and 17 uM respectively) WO 4 - , Ni +2 , Co +2 was selected for the PC12 cell exposure condition. In addition to testing the complete alloy the individual metal ions and metal ion combinations (W/Ni, W/Co, Co/Ni) were also tested at the indicated concentrations. PC12 cells were incubated in the presence of neuronal growth factor and the metal ions (or without metals as a negative control) for 24 hours followed by RNA extraction. Each test condition was performed in triplicate wells and the entire experiment was repeated for a total of 4 replicates. For the microarray analysis, Affymetrix Rat Genome 230 2.0 whole genome oligonucleotide arrays were used. Expression data was analyzed using JMP Genomics 4.1 (SAS) software. Our preliminary findings suggest that there are differences between the gene expression profiles of the single metal and alloy treatments. The changes in gene expression as it relates to the presence of tungstate will be discussed. 1384 DIFFERENT SUSCEPTIBILITIES TO MEHG-INDUCED CELL DEATH BETWEEN NON-NEURONAL AND NEURONAL CELLS. V. Vidal 1 , S. M. Fox 2 and W. D. Atchison 2 . 1 University of Puerto Rico at Cayey, Cayey, Puerto Rico and 2 Pharmacology and Toxicology, Michigan State University, East Lansing, MI. Methylmercury (MeHg) is a highly lipophilic environmental neurotoxicant that causes selective damage in both the central and peripheral nervous system. Among the many cellular targets associated with the effects of MeHg are voltage-gated Ca 2+ channels. The action of MeHg is identified to be a direct interaction with the Ca 2+ channels subunits as well as an interaction with intracellular signaling pathways that modulate their activity. The goals of this project were to determine the difference in susceptibility to MeHg-induced cell death between undifferentiated PC12 cells, a neuronal cell line, and human embryonic kidney (HEK) cells, a non-neuronal cell line, as well as, to study the contribution of the L-type Ca 2+ channel (Cav 1.2) to MeHg-induced cell death. PC12 cells express Cav1.2 abundantly- especially in the undifferentiated state; HEK cells do not. HEK cells were transiently transfected with Cav 1.2 (HEK-α1C) in order to assess the contribution of the L-type Ca 2+ channel in the absence of other neuronal targets of MeHg. The transfection utilized expression cDNA plasmids containing α1C, β3, and α2δ Ca 2+ channel
subunits. Each cell type was treated with 0.5, 1, 2, or 5 μM MeHg for 2 h and cell viability was measured 24 h later using trypan blue. Concentration- dependence of cytotoxicity was seen in each cell type. PC12 cells had a greater reduction in cell viability than both HEK and HEK-α1C after treatment with MeHg. At 0.5 and 1 μM MeHg there was little change in viability in either cell type. At 2 μM MeHg cell viability in both HEK and HEK-α1C cells was ~97% while it was 88% in PC12 cells. Cell viability was 85%, 90% and 80% in HEK, HEK-α1C, and PC12 cells, respectively, after treatment with 5 μM MeHg. Using this model system neuronal cells are more susceptible to MeHg-induced cell death than non-neuronal cells. Supported by 5R01-ES03299 and 5R25NS065777. 1385 EFFECTS OF ACUTE EXPOSURE TO METHYLMERCURY ON INTRACELLULAR CA 2+ IN PRIMARY CEREBELLAR GRANULE CELLS OF TOTTERING AND LETHARGIC MICE. B. Marrero-Rosado1 and W. D. Atchison2 . 1Genetics Program, Michigan State University, East Lansing, MI and 2Pharmacology and Toxicology, Michigan State University, East Lansing, MI. Methylmercury (MeHg), preferentially affects cerebellar granule cell (CGC) function both in vivo and in vitro. In CGCs MeHg disrupts intracellular Ca2+ (Ca2+ i ) in a biphasic manner involving distinct effects on Ca2+ i stores, and extracellular entry. CGCs contain several types of voltage-gated Ca2+ channels (VGCCs), all of which are susceptible to block by MeHg, but also contribute to the increased [Ca2+ ] i in CGCs. The possibility that certain VGCC subtypes may facilitate effects of MeHg in native cells has not been examined. In vitro acute exposure to MeHg and single cell imaging was used to examine [Ca2+ ] i homeostasis in CGCs of two naturally-occurring mutants of the P/Q-type VGCC (tottering-tg and lethargic-lh) mice. Tg results from a spontaneous missense mutation in the gene Cacna1a that codes the pore-forming α1A subunit of P/Q-type VGCCs. To compensate, tg CGCs upregulate N-type VGCCs. Lh mice have a 4-base pair insertion in the β4 subunit gene, Cacnb4, truncating the subunit, preventing binding to α1A . Lh mice compensate by upregulating β1B and β3 . CGCs were isolated at PND 7, loaded with Fura-2 and acutely exposed to 0.3, 1, or 3 μM MeHg. Onset times of the 2 phases of increased [Ca2+ ] i were compared among genotypes. Tg CGCs do not differ significantly from WT for onset of either phase of MeHg-induced increased [Ca2+ ] i , but lh CGCs reach both phases more rapidly than their WT littermates. To investigate whether adult tg CGCs would respond differently to MeHg, cells were artificially matured by lowering medium [K + ]. Both phases of [Ca2+ ] i increase were now significantly delayed in onset. This raises the possibility of a gene/environment contribution to the effects of MeHg in cerebellum. Supported by R01ES03299, and R25NS065777. 1386 METHYLMERCURY DECREASES NEURONAL MIGRATION, VINCULIN LEVELS, AND LOCATION IN FOCAL ADHESION OF A NEUROBLASTOMA CELL LINE. D. Albores-Garcia1 , L. C. Acosta-Saavedra1 , E. K. Silbergeld2 and E. S. Calderon-Aranda1 . 1Department Toxicologia, Cinvestav, Mexico, Mexico and 2BSPH, Johns Hopkins University, Baltimore, MD. Methylmercury (MeHg) is an organometal that inhibits neuronal migration during the central nervous system development, and for which the molecular mechanisms are not completely defined. The neuronal migration involved the assembly and disassembly of focal adhesions (FA), conformed by a complex of proteins that include vinculin, paxillin and FAK (focal adhesion kinase), as well as kinases like MAPKs (mitogen associated protein kinases). Our group has shown in primary cultures of mouse cerebellum, that MeHg decreases the phosphorylation of ERK, p38 and JNK, as well as paxillin levels, effects that were related with inhibition of neurons migration. The objective of this work was to study the effect of MeHg on neuronal migration, vinculin levels, and vinculin location in focal adhesion in a human neuroblastoma cell line. Methods. Human neuroblastoma cell line SH-SY5Y activated or non activated to migration with 50ng/mL PDGF (platelet-derived growth factor), were treated with 100nM of MeHg, and cell migration was evaluated by Scratch method, vinculin levels by Western Blot and vinculin location in FA (determined as vinculin-FAK co-location) was by confocal microscopy. Results showed that MeHg decreases migration induced by PDGF at 6 h of treatment, as well basal migration in non activated cells. MeHg, both in absence and presence of PDGF, decreased the vinculin levels compared with their respective controls. MeHg decrease size of adhesion points corresponding to vinculin and FAK, and its co-location, compared with non activated control; in activated cells MeHg decreased the number and size of FA with vinculin, compared with levels of vinculin in FA adhesion induced by PDGF. These results suggest that inhibition of neuronal migration by MeHg involves the alteration of focal adhesions, and that further study is required to establish the effect of MeHg on molecules that are involved and/or regulated the assembly and disassembly of FA adhesions. This work was supported by Conacyt-46297. 1387 EFFECT OF METHYLMERCURY ON THE NEURONAL MIGRATION AND ON ACTIVITY OF FAK IN HUMAN NEUROBLASTOMA CELLS. G. T. Rodriguez-Kessler 1 , D. Albores-Garcia 1 , L. C. Acosta-Saavedra 1 , B. Luque 1 , D. Arias-Salvatierra 1 , E. K. Silbergeld 2 and E. S. Calderon-Aranda 1 . 1 Toxicologia, Cinvestav, Mexico, Mexico and 2 BSPH, Johns Hopkins University, Baltimore, MD. Methylmercury (MeHg)inhibits neuronal migration but molecular mechanisms are poorly understood. Neuronal migration is a multistep process with rapid changes that involved assembly and disassembly of focal adhesions (FA). Focal adhesion kinase (FAK) is an essential component of the FA that regulates the recruitment and activation of other proteins. ERK and JNK (MAPKs)regulate interactions of FAK with other proteins like paxillin (Pax), and the assembly and disassembly of FA. We have shown that exposure to MeHg decreases the phosphorylation of MAPKs, the levels of Pax and the neuronal migration in cerebellar primary cultures; we established that MeHg reduces the levels of vinculin, another key element of FA, and inhibits neuronal migration of the human neuroblastoma cells. Although these data partly explain the mechanism by which MeHg inhibits neuronal migration, it is necessary to evaluate the effect of MeHg on critical proteins involved in regulation of AF. The objective in this work is to study the effect of MeHg on neuronal migration, the phosphorylation of critical residues for the activation of FAK and for its interaction with Pax, the role of ERK and JNK in these effects, as well as the relationship of all these. Methods. In SH-SY5Y cells activated or not to migration with PDGF (50ng/mL) the effect of 100ng/mL of MeHg is assess on cell migration by scratch assay, phosphorylation of FAK is by Western-blot, and role of ERK and JNK in these effects is evaluated using specific inhibitors.Results shown that MeHg decreases migration induced by PDGF,as well as the basal migration in non activated cells.With inhibitors of ERK and JNK was determined that both kinases are involved in cell migration induced by PDGF.Experiments to evaluate the MeHg effect on FAK and Pax phosphorylation are in progress. This work was supported by Conacyt-46297. 1388 DIFFERENTIAL EFFECTS OF NEUROTOXIC MERCURIALS ON ANGIOGENESIS (AG). M. Nash 1 , E. Robinson 1 , B. J. Zaffo 1 , S. Obhan 2 , N. F. Alrowaily 1 , L. A. Shaiba 1 , S. A. Mousa 2 and H. A. El-Fawal 1 . 1 Health Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY and 2 Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY. The elaboration of vascular beds, AG, is essential during neurogenesis. Compromised neural AG in adult models has been shown to result in neuropathy and neurodegeneration. Mercurial compounds (Hg), organic [methy (MeHg) and ethyl (EHg)] and inorganic [mercuric chloride (HgCl)] are known developmental neurotxicants. However, their effects on AG as a contributing factor in inducing neurotoxicity have not been investigated. The effects of equimolar concentrations (40 nM) of these compounds on AG, in the presence or absence of 40 μg vascularendothelium growth factor (VEGF) were investigated in the 10 day chick chorioallontoic membrane (CAM) model. Test compounds placed on coverslips were added onto the membrane of CAM and harvested after 3 days of incubation under optimal condition of O 2 /CO 2 and humidity to visualize and quantify developing vessel length (L), number of branch points (B) and perfusion area (A). All Hg compounds reduced B by 40-60% with the greatest reduction seen with HgCl. Significant (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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Page 255 and 256: have now compared the IC50 values b
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1613 AN INVESTIGATION OF THE CLEARA
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its nuclear translocation was reduc
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were collected from TK animals at d
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egulated targets were selected for
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U/L after tetracycline. Minocycline
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peri-pubertal FasL-/- mice show a d
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showed similar levels of apoptosis
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1676 TWO BIOMARKERS FOR EVALUATION
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motifs selected. This system was ap
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1693 VOC SERUM LEVELS IN THE GENERA
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1702 DOES THE CLOCK MAKE THE POISON
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those with high nickel content are
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isk assessment. However, unique cha
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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
Page 403 and 404:
are a family of phase-II biotransfo
Page 405 and 406:
ous labs. As a result of positive s
Page 407 and 408:
down the doses may produce more tox
Page 409 and 410:
spectively. Below 100 mg/l of gemfi
Page 411 and 412:
1900 GENERATION OF PRECISION CUT LI
Page 413 and 414:
iomarkers or observation of lesions
Page 415 and 416:
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
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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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