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shown by the increased number of cells positive for EdU-staining and the upregulation of Cyclin D3 protein. Conversely, exposure to PCB 153 or 180 resulted in a lower number of EdU-positive cells with no changes in the expression of Cyclin D3 as compared to control cells. Experiments with Fucci transfection confirmed the observed effects on proliferation. In agreement, MeHg increased the number of NSCs exhibiting spontaneous Ca2+ activity, whereas both PCBs caused a significant decrease. q-PCR analyses pointed to an involvement of Notch signaling in the observed effects of MeHg and PCBs on NSCs differentiation. Alterations in neuronal differentiation may partially explain the adverse impact of MeHg and PCBs on the developing nervous system. 2623 NON-DIOXIN-LIKE POLYCHLORINATED BIPHENYLS (PCBS ) ENHANCE DENDRITIC GROWTH IN CULTURED HIPPOCAMPAL NEURONS VIA RYANODINE RECEPTOR (RYR)-DEPENDENT ACTIVATION OF CALCIUM-DEPENDENT SIGNALING PATHWAYS. D. D. Bose 1 , D. Yang 1 , G. Wayman 2 , A. Lesiak 2 , D. Bruun 1 , I. N. Pessah 1 and P. J. Lein 1 . 1 Veterinary Molecular Biosciences, University of California, Davis, Davis, CA and 2 Veterinary and Comparative Anatomy, Washington State University, Pullman, WA. Exposure of the developing brain to PCBs is linked to cognitive deficits in humans and experimental animals, but the mechanism(s) underlying the developmental neurotoxicity of these compounds remain speculative. Our previous in vivo studies of rats exposed developmentally to PCBs demonstrated that PCBs disrupt spatial learning and memory coincident with altered dendritic growth and ryanodine receptor (RyR) expression. Here we show that PCB effects on dendritic growth and RyRs are causally related. We quantified dendritic growth in cultured hippocampal neurons transfected with a GFP-tagged MAP2 construct following a 48h exposure to either PCB95, a non-coplanar PCB congener that is a potent activator of the RyR, or PCB66 a coplanar PCB congener with no activity at the RyR. PCB95, but not PCB66, significantly enhanced dendritic growth. The dendrite promoting activity of PCB95 was evident at concentrations as low as 2pM and was completely blocked by FLA365, a RyR channel blocker and by siRNA knockdown of RyRs. Acute exposure to PCB95 (200nM) increased the frequency and amplitude of spontaneous Ca 2+ oscillations in hippocampal neurons whereas no such effect was observed with PCB66 (200nM) and vehicle (DMSO). In neurons exposed to PCB95 for 48hr, the amplitude of evoked Ca 2+ transients decreased in a concentration-dependent manner. Genetic and pharmacological blockade of Ca 2+ signaling molecules implicated in activity-dependent dendritic growth inhibited PCB95-induced dendritic growth. These data demonstrate that PCB activation of RyR modulates Ca 2+ -dependent signaling pathways that regulate dendritic plasticity, and suggest that non-coplanar PCBs may be useful probes for studying the role of the RyR in activity-dependent dendritic growth. This work supported by NIH grants ES014901 (PJL and INP) and MH86032 (GAW). 2624 ENANTIOSELECTIVE EFFECTS OF PCB136 ON DENDRITIC GROWTH ARE RYANODINE RECEPTOR-DEPENDENT. D. Yang 1 , I. Kania-Korwel 2 , D. Bose 1 , A. Ghogha 1 , I. Pessah 1 , H. Lehmler 2 and P. Lein 1 . 1 Veterinary Medicine, Molecular Biosciences, University of California Davis, Davis, CA and 2 Occupational & Environmental Health, University of Iowa, Iowa City, IA. Polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyR), and experimental evidence indicates this activity contributes to PCB developmental neurotoxicity. Many of these ortho-substituted congeners display axial chirality and we have previously reported that chiral PCB atropisomers differentially sensitize RyR. In this study, we test the hypothesis that chiral PCB136 enantioselectively influences RyR-mediated dendritic growth. Primary cultured rat hippocampal neurons were exposed to purified PCB136 atropisomers for 48 hr beginning on day 9 in vitro. (-)-PCB136, which sensitizes RyR, enhances dendritic growth at concentrations ranging from 0.1nM to 1μM, and this effect is blocked by the RyR specific antagonist FLA365. In contrast, (+)-PCB136, which lacks activity towards RyR, has no effect on dendritic growth. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB136 atropisomers in cell media and cell pellets indicates that the enantioselective effects on dendritic growth are not due to enantioselective partitioning of PCB136 into cells. Imaging of cultured hippocampal neurons loaded with the Ca2+-sensitive dye 562 SOT 2011 ANNUAL MEETING Fluo-4 indicates that (-)- but not (+)-PCB136 increases the frequency of spontaneous Ca2+ oscillations in cultured hippocampal neurons, which is consistent with the finding that (-)- but not (+)-PCB136 increases electrical activity in neurons plated on microelectrode arrays. These data support the hypothesis that enantioselective effects on RyR mediate the enantioselective effects of PCB136 on dendritic growth, and suggest that the significant variability in enantiomeric enrichment of chiral PCBs in the human population may be a significant factor in determining the risk for adverse neurodevelopmental outcomes following PCB exposure (supported by NIH grant ES017425). 2625 POLYCHLORINATED BIPHENYLS (PCBS ) ALTER GLUTAMATE RELEASE FROM PRESYNAPTIC NERVE TERMINALS ISOLATED FROM THE RAT HIPPOCAMPUS INDEPENDENT OF ARYL HYDROCARBON RECEPTOR (AHR) MEDIATED GENE TRANSCRIPTION. N. Newman and F. Schanne. Pharmaceutical Sciences, St. John’s University, Queens, NY. Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants known to elicit a myriad of toxicological responses. There are 209 possible PCB congeners, depending upon the number of chlorines present and their position on either of the phenyl rings. PCBs were produced as complex mixtures of dioxin-like coplanar and non-dioxin-like non-coplanar congeners. The coplanar congeners are commonly associated with cancer and other health risks whereas the non-coplanar congeners, especially those that are di-ortho- substituted, are more often associated with neurotoxicity. 3,3′,4,4′-Tetrachlorobiphenyl (PCB 77), a dioxin like meta- and para-substituted co-planar congener, is known to be neuroactive in vitro. It has been suggested that, contrary to the notion that co-planar PCBs require aryl hydrocarbon receptor (Ahr) mediated gene transcription to exert their toxicity, PCB 77 exhibits Ahr independent neurotoxicity. This study analyzed the effects of PCB 77 on the evoked release of glutamate from pre-synaptic nerve terminals (synaptosomes) isolated from the CA1 region of the rat hippocampus. Evoked release of glutamate is central to synaptic transmission and is modified as a component of synaptic plasticity. Release of endogenous glutamate was estimated by measuring the fluorescence of NADPH resulting from the reduction of NADP+ by glutamate dehydrogenase. PCB 77 significantly enhanced glutamate release at micromolar treatment concentrations. Treatment with the non-coplanar diortho substituted 2,2’,5,5’ Tetrachlorobiphenyl (PCB 52) also significantly enhanced glutamate release. However, when these PCBs were combined, glutamate release was significantly diminished suggesting that co-planar and non-coplanar PCBs impact this process via different mechanisms. As synaptosomes are devoid of a nucleus, these observations confirm that the effects of these PCBs on synaptosomal glutamate release are independent of Ahr mediated gene transcription. 2626 NEUROBEHAVIORAL AND TRANSCRIPTIONAL CONSEQUENCES OF ESTROGEN RELATED RECEPTOR GAMMA ACTIVATION BY LOW-DOSE BISPHENOL A EXPOSURE DURING NEUROGENESIS. K. S. Saili, M. M. Corvi, J. Przybyla, J. K. LaDu, K. A. Anderson and R. L. Tanguay. Department of Environmental & Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR. Bisphenol A (BPA) is detectable in the serum and breast milk of pregnant and nursing women. Risk to fetuses and infants is a concern based on evidence from rodent studies that exposure to low levels of BPA during critical periods of central nervous system (CNS) development leads to persistent behavioral impairments. The mechanism by which BPA impairs CNS development is unclear, but likely involves both classical estrogen receptor (ER) and estrogen related receptor (ERR) signaling pathways. BPA’s high binding affinity for estrogen related receptor gamma (ERRγ) suggests a central role for this orphan nuclear receptor. To assess the effects of BPA on CNS development, zebrafish were exposed to concentrations below the no observed adverse effect concentration (NOAEC) during early neurogenesis (10–58 hours post fertilization, hpf) and behavior endpoints were assessed at 120 hpf. Increased locomotor activity was measured in larvae exposed to 0.1 μM (corresponding to a human-relevant tissue dose
exhibited a hyperactive phenotype, behavior in BPA-exposed embryos injected with ERRγ MO was indistinguishable from unexposed control morphants. To further characterize the transcriptional events associated with the hyperactive phenotype, transcripts associated with ER or ERR signaling were measured by qRT-PCR following BPA, E2, or GSK4716 exposure. Taken together, we have identified a role for ERRγ in mediating the neurobehavioral toxicity of developmental BPA exposure. This research was supported in part by NIEHS T32ES7060, ES00210, and an EPA STAR Graduate Fellowship to KSS. 2627 EFFECTS OF RADIO FREQUENCY RADIATION EXPOSURE FROM MOBILE PHONES ON BRAIN MICROVESSEL ENDOTHELIAL CELLS, A MODEL OF BLOOD BRAIN BARRIER: AN IN VITRO STUDY. E. Cuevas 1 , S. M. Lantz 1 , W. J. Trickler 1 , B. R. Robinson 1 , G. D. Newport 1 , P. C. Howard 2 , N. J. Walker 3 , M. Wyde 3 , A. Desta 4 , M. G. Paule 1 and S. F. Ali 1 . 1 Neurochemistry Laboratory, Division of Neurotoxicology, NCTR/U.S. FDA, Jefferson, AR, 2 Office of Scientific Coordination, NCTR/U.S. FDA, Jefferson, AR, 3 National Toxicology Program, NIEHS, Research Triangle Park, NC and 4 ODE, CDRH/U.S. FDA, Sliver Spring, MD. The association between exposure to radio frequency (RF) energy similar to that emitted by mobile phones and potential adverse effects to the central nervous system, including blood-brain barrier (BBB) dysfunction, neurotoxicity and brain tumors continue to be an area of scientific controversy. We have designed studies to test the effects of RF energy exposures on rat and bovine primary brain microvessel endothelial cells (BMEC). BMEC cells were isolated from fresh rat and bovine cerebral cortices and cultured in 35 mm petri dishes (12-14 days). The BMEC (80% confluent) were exposed to RF energy at the specific absorption rate (SAR) levels of 5.04 W/kg (rat) or 5.98 W/kg (bovine) (600sec - 60sec; on-off cycle) for 4, 8, or 24 hours. (The maximum permissible SAR from mobile phones in US is 1.6 W/kg). Cell viability was evaluated by lactate dehydrogenase (LDH) assay and MTT [3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Nitric oxide (NO) changes were determined by Griess reaction. Heat shock proteins (HSPs), receptor for advanced glycation end products (RAGE) expression, and inflammatory makers [tumor necrosis factor-alpha (TNFα), interleukin 1 beta (IL-1β), interleukin 2 (IL-2), and prostaglandin E2 (PGE-2)] levels were evaluated. Under these conditions, SAR exposures produced no cytotoxic changes as measured by LDH, MTT and NO, however, the same SAR exposure increased activation of HSP27, HSP90, and RAGE, and changes in several inflammatory markers (TNFα, IL-1β, IL-2, and PGE-2) at 8 and 24 hours. These preliminary results indicate that SAR exposure activates HSPs family, neuroinflammatory markers which may reflect early intracellular signaling pathways and may ultimately alter BBB integrity. These studies were supported by NTP/NCTR IAG 224-07-007. 2628 REARING CONDITIONS DIFFERENTIALLY AFFECT THE LOCOMOTOR BEHAVIOR OF LARVAL ZEBRAFISH, BUT NOT THEIR RESPONSE TO VALPROATE-INDUCED DEVELOPMENTAL NEUROTOXICITY. D. Zellner 1 , B. Padnos 2 , D. L. Hunter 2 , R. C. MacPhail 3 and S. Padilla 2 . 1 Meredith College, Raleigh, NC, 2 ISTD, U.S. EPA, Res. Tri. Pk., NC and 3 TAD, U.S. EPA, Res. Tri. Pk., NC. Zebrafish (Danio rerio) are widely used in developmental research, but little is known about the role environment may play in their development. Zebrafish are a highly social organism; thus exposure to or isolation from social environments may have profound effects. Details of rearing conditions are often sparse in the literature. This study compared (1) the activity of larval zebrafish that were raised individually or in groups, and (2) the effect of the developmental neurotoxicant valproate. We randomly assigned embryos to isolative or inclusive social environments from 0 to 5 days post fertilization (dpf), while treating them with or without valproate (50 uM) from 0-2 dpf resulting in a total of four groups (group control, group treated, single control, single treated). At 5 dpf all embryos were transferred to singly-housed environments where they remained through locomotor testing (alternating periods of light and dark) conducted on day 6. Larvae that had been raised in groups had higher levels of activity than larvae that had been raised individually, but only in the dark periods. Valproate increased activity in the dark in both the singly and group housed groups. Further analyses indicated rearing condition did not significantly affect larval responses to valproate. These results indicate that rearing conditions affect behavioral development of zebrafish larvae, but that rearing conditions may not affect the effect of a developmental neurotoxicant. This is an abstract of a proposed presentation: the information does not necessarily reflect EPA policy. 2629 ASSESSMENT OF CHEMICAL EFFECTS ON NEURITE OUTGROWTH, NEURONAL POLARIZATION, AND SYNAPTOGENESIS IN RAT CORTICAL NEURONS USING HIGH CONTENT IMAGE ANALYSIS. B. L. Robinette, J. A. Harrill and W. R. Mundy. Integrated Systems Toxicology Division, NHEERL, U.S. EPA, Research Triangle Park, NC. There is a need for efficient, cost-effective methods for screening and prioritization of potential developmental neurotoxicants. One approach uses in vitro cell culture models that can recapitulate the critical processes of nervous system development. In vitro, primary cultures of neocortex undergo a series of morphological changes including neurite outgrowth, polariation of neurites and synaptogenesis similar to that observed in vivo. In the present work, primary cultures were prepared from rat neocortex in a 96-well plate format. A combination of immunocytochemical labeling and high-content image analysis (HCA) protocols were developed in order to quantify the time course of neurite outgrowth (βIII-tubulin), neuronal polarization (βIII-tubulin and MAP2 or neurofilament) and synapse formation (MAP2 and synapsin). Neurite outgrowth occurred rapidly: 75 % of neurons developed neurites by 24 h. At this time, ~20% of neurons were axon bearing. An increase in total neurite length continued up 5 days in vitro (DIV), at which time a change in the cytoplasmic distribution if MAP2 was observed. The ratio of βIII-tubulin and MAP2 labeled neurite lengths (NPR) increased from 1.35 to 2.12 between 24 and 120 h, indicative of neuronal polarization. An increase in synapse number was observed between 6 and 15 DIV. The concentration-response of model chemicals known to inhibit each process was then examined. K252a (0.01 - 1 μM) applied at 2 h inhibited total neurite outgrowth (20 %), specifically axon outgrowth (97 %), at 24 h and inhibited neuronal polarization at 120 h (NPR = 1.3). In addition, mevastatin applied at 9 DIV (0.3 – 30 μM) decreased synapse number at 15 DIV (~35 %). Effects occurred in the absence of overt cytotoxicity. These data demonstrate that HCA using a single culture system can be used to screen for chemical effects on multiple processes of nervous system development. This abstract does not necessarily reflect USEPA policy. 2630 INITIATING EFFECTS OF METHYLEUGENOL IN RAT LIVER. M. J. Iatropoulos, A. M. Jeffrey, J. Duan and G. M. Williams. Department of Pathology, New York Medical College, Valhalla, NY. Methyleugenol (ME), a constituent of basil, is hepatocarcinogenic in rodents. To study initiating effects of ME in rat liver, groups of male F344 rats were administered by gavage 0 (control, C), 62 (low dose, LD), 125 (mid dose, MD), or 250 (high dose, HD) mg/kg bw/dose, 3 times/week for 8 or 16 weeks (providing cumulative doses (CD) of 185, 275 or 750 mg/kg bw/week similar to the weekly CD of the NTP ME bioassay). After week 16, half of the rats were fed 500 ppm phenobarbital in the diet (+PB), and the rest were maintained on C diet (-PB) for 24 weeks. At 8 weeks, the MD and HD groups had bw reductions, and group relative liver weight increases. 32 P-nucleotide postlabeling (NPL) revealed 3 adducts in the livers of all ME groups. The hepatic DNA-adduct values were dose related and were increased in all ME groups compared to C. PCNA immunohistochemistry (IHC) revealed that the group hepatocellular replicating fraction (RF) in all ME groups was increased compared to C. Only the HD rats had hepatocellular altered foci (HAF), identified by glutathione S-transferase-placental form IHC. At 16 weeks, there were no differences in bw between groups and no changes in measured serum liver enzymes. All ME groups had dose-related increases in DNA adducts in both liver and white blood cells (WBCs) compared to C, although the WBC levels were 1% of those of the liver. The group RF and HAF in all ME groups were increased compared to C in a dose-related pattern. At the end of the promotion/maintenance phase (weeks 16-40), the NPL values in both ME/+PB and ME/-PB groups were lower than the respective 16-wk NPL values, indicating DNA repair. HAF were evident in all +PB groups, including C. The multiplicity and severity of HAF was similar between C (1 and 1+, respectively) and LD (2 and 1+) while those of the MD (8.3 and 3+) and HD (28.8 and 4+) were increased. Hepatocellular adenomas were evident in a dose-related pattern in both +PB and -PB MD and HD groups, attaining higher multiplicity and severity in the +PB groups. Thus, ME had initiating activity and the LD was a NOAEL for pre- and neoplasia, but not for DNA adducts. SOT 2011 ANNUAL MEETING 563
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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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exposure to both ATR and DACT has a
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third tetratricopeptide repeats (TP
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7d. 28d after TMT injury there was
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subunits. Each cell type was treate
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1394 COMPARATIVE EFFECTS OF METHYLM
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1403 GENOTOXICITY AND PRE-NEOPLASTI
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vated only in high-dose-treated ani
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1421 DOSE-RESPONSE OF NAPHTHALENE-I
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cisplatin; 1.2-, 1.9- and 2.9-fold
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Day 11 and started to recover on Da
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1448 DEVELOPMENT OF A METHOD FOR QU
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1457 GLOBAL GENE PROFILING REVEALS
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cluding mouse and human macrophage,
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model of lung inflammation and host
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1484 NANOTOXICOLOGY AND NANOHEALTH
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throughput in vitro approach was us
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1502 IMMUNOLOGICAL ASPECTS OF AN AN
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(CIA) and the Streptococcal cell wa
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sitizers were 100% concordant among
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1530 MINIMAL RISK LEVELS FOR STYREN
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ical groups in the field of regulat
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vitro with this potentially insect-
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their performance on toxicological
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need for a better understanding of
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1577 AN IN VITRO MODEL SYSTEM FOR A
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gene expression post-transcriptiona
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1595 GENE EXPRESSION PROFILE OF RAT
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to confirm a hepatotoxic property o
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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
Page 395 and 396:
1825 EFFECTS OF METABOLISM BY INTES
Page 397 and 398:
cyanoacetic acid increased 2-3 fold
Page 399 and 400:
1845 IS THE PROMISCUITY OF THE ARYL
Page 401 and 402:
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: histopathological or biochemical ev
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 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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